ID ARX_HUMAN Reviewed; 562 AA. AC Q96QS3; DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 184. DE RecName: Full=Homeobox protein ARX; DE AltName: Full=Aristaless-related homeobox; GN Name=ARX; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=12359145; DOI=10.1016/s1096-7192(02)00126-9; RA Ohira R.H., Zhang Y.H., Guo W., Dipple K., Shih S., Doerr J., Huang B.-L., RA Fu L., Abu-Khalil A., Geschwind D., McCabe E.; RT "Human ARX gene: genomic characterization and expression."; RL Mol. Genet. Metab. 77:179-188(2002). RN [2] RP VARIANT DEE1 ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS. RX PubMed=12376946; DOI=10.1002/ajmg.10714; RA Turner G., Partington M., Kerr B., Mangelsdorf M., Gecz J.; RT "Variable expression of mental retardation, autism, seizures, and dystonic RT hand movements in two families with an identical ARX gene mutation."; RL Am. J. Med. Genet. 112:405-411(2002). RN [3] RP VARIANTS XLID29 PRO-33 AND SER-286, AND TISSUE SPECIFICITY. RX PubMed=11971879; DOI=10.1093/hmg/11.8.981; RA Bienvenu T., Poirier K., Friocourt G., Bahi N., Beaumont D., Fauchereau F., RA Ben-Jeema L., Zemni R., Vinet M.-C., Francis F., Couvert P., Gomot M., RA Moraine C., van Bokhoven H., Kalscheuer V., Frints S., Gecz J., Ohzaki K., RA Chaabouni H., Fryns J.-P., Desportes V., Beldjord C., Chelly J.; RT "ARX, a novel Prd-class-homeobox gene highly expressed in the RT telencephalon, is mutated in X-linked mental retardation."; RL Hum. Mol. Genet. 11:981-991(2002). RN [4] RP FUNCTION, VARIANTS DEE1 ALA-ALA-ALA-ALA-ALA-ALA-ALA-115 INS; RP ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS AND LEU-353, VARIANT PRTS RP ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-155 INS, AND TISSUE SPECIFICITY. RX PubMed=11889467; DOI=10.1038/ng862; RA Stroemme P., Mangelsdorf M.E., Shaw M.A., Lower K.M., Lewis S.M.E., RA Bruyere H., Luetcherath V., Gedeon A.K., Wallace R.H., Scheffer I.E., RA Turner G., Partington M., Frints S.G.M., Fryns J.-P., Sutherland G.R., RA Mulley J.C., Gecz J.; RT "Mutations in the human ortholog of aristaless cause X-linked mental RT retardation and epilepsy."; RL Nat. Genet. 30:441-445(2002). RN [5] RP FUNCTION, AND VARIANTS LISX2 HIS-332 AND GLN-343. RX PubMed=12379852; DOI=10.1038/ng1009; RA Kitamura K., Yanazawa M., Sugiyama N., Miura H., Iizuka-Kogo A., Kusaka M., RA Omichi K., Suzuki R., Kato-Fukui Y., Kamiirisa K., Matsuo M., Kamijo S., RA Kasahara M., Yoshioka H., Ogata T., Fukuda T., Kondo I., Kato M., RA Dobyns W.B., Yokoyama M., Morohashi K.; RT "Mutation of ARX causes abnormal development of forebrain and testes in RT mice and X-linked lissencephaly with abnormal genitalia in humans."; RL Nat. Genet. 32:359-369(2002). RN [6] RP FUNCTION, VARIANTS LISX2 PRO-332; HIS-332; GLN-343; ARG-353 AND THR-521, RP AND VARIANT ACCAG ASN-333. RX PubMed=14722918; DOI=10.1002/humu.10310; RA Kato M., Das S., Petras K., Kitamura K., Morohashi K., Abuelo D.N., RA Barr M., Bonneau D., Brady A.F., Carpenter N.J., Cipero K.L., Frisone F., RA Fukuda T., Guerrini R., Iida E., Itoh M., Lewanda A.F., Nanba Y., Oka A., RA Proud V.K., Saugier-Veber P., Schelley S.L., Selicorni A., Shaner R., RA Silengo M., Stewart F., Sugiyama N., Toyama J., Toutain A., Vargas A.L., RA Yanazawa M., Zackai E.H., Dobyns W.B.; RT "Mutations of ARX are associated with striking pleiotropy and consistent RT genotype-phenotype correlation."; RL Hum. Mutat. 23:147-159(2004). RN [7] RP FUNCTION, CHARACTERIZATION OF VARIANT ACCAG ASN-333, CHARACTERIZATION OF RP VARIANT DEE1 LEU-353, CHARACTERIZATION OF VARIANTS LISX2 PRO-332; GLN-343 RP AND ARG-353, AND MUTAGENESIS OF ARG-358 AND ARG-379. RX PubMed=22194193; DOI=10.1093/hmg/ddr601; RA Shoubridge C., Tan M.H., Seiboth G., Gecz J.; RT "ARX homeodomain mutations abolish DNA binding and lead to a loss of RT transcriptional repression."; RL Hum. Mol. Genet. 21:1639-1647(2012). RN [8] RP VARIANT DEE1 LEU-353. RX PubMed=27864847; DOI=10.1002/humu.23149; RG Clinical Study Group; RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D., RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S., RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.; RT "Diagnostic targeted resequencing in 349 patients with drug-resistant RT pediatric epilepsies identifies causative mutations in 30 different RT genes."; RL Hum. Mutat. 38:216-225(2017). RN [9] RP FUNCTION, CHARACTERIZATION OF VARIANTS LISX2 PRO-332; GLN-343 AND ARG-353, RP CHARACTERIZATION OF VARIANT ACCAG ASN-333, AND MUTAGENESIS OF ARG-358 AND RP ARG-379. RX PubMed=31691806; DOI=10.1093/hmg/ddz254; RA Poeta L., Padula A., Attianese B., Valentino M., Verrillo L., Filosa S., RA Shoubridge C., Barra A., Schwartz C.E., Christensen J., van Bokhoven H., RA Helin K., Lioi M.B., Collombat P., Gecz J., Altucci L., Di Schiavi E., RA Miano M.G.; RT "Histone demethylase KDM5C is a SAHA-sensitive central hub at the RT crossroads of transcriptional axes involved in multiple neurodevelopmental RT disorders."; RL Hum. Mol. Genet. 28:4089-4102(2019). RN [10] RP VARIANT VAL-370. RX PubMed=35840571; DOI=10.1038/s41467-022-31566-z; RA El Chehadeh S., Han K.A., Kim D., Jang G., Bakhtiari S., Lim D., Kim H.Y., RA Kim J., Kim H., Wynn J., Chung W.K., Vitiello G., Cutcutache I., Page M., RA Gecz J., Harper K., Han A.R., Kim H.M., Wessels M., Bayat A., Jaen A.F., RA Selicorni A., Maitz S., de Brouwer A.P.M., Silfhout A.V., Armstrong M., RA Symonds J., Kuery S., Isidor B., Cogne B., Nizon M., Feger C., Muller J., RA Torti E., Grange D.K., Willems M., Kruer M.C., Ko J., Piton A., Um J.W.; RT "SLITRK2 variants associated with neurodevelopmental disorders impair RT excitatory synaptic function and cognition in mice."; RL Nat. Commun. 13:4112-4112(2022). CC -!- FUNCTION: Transcription factor (PubMed:22194193, PubMed:31691806). CC Binds to specific sequence motif 5'-TAATTA-3' in regulatory elements of CC target genes, such as histone demethylase KDM5C (PubMed:22194193, CC PubMed:31691806). Positively modulates transcription of KDM5C CC (PubMed:31691806). Activates expression of KDM5C synergistically with CC histone lysine demethylase PHF8 and perhaps in competition with CC transcription regulator ZNF711; synergy may be related to enrichment of CC histone H3K4me3 in regulatory elements (PubMed:31691806). Required for CC normal brain development (PubMed:11889467, PubMed:12379852, CC PubMed:14722918). Plays a role in neuronal proliferation, interneuronal CC migration and differentiation in the embryonic forebrain (By CC similarity). May also be involved in axonal guidance in the floor plate CC (By similarity). {ECO:0000250|UniProtKB:O35085, CC ECO:0000269|PubMed:11889467, ECO:0000269|PubMed:12379852, CC ECO:0000269|PubMed:14722918, ECO:0000269|PubMed:22194193, CC ECO:0000269|PubMed:31691806}. CC -!- INTERACTION: CC Q96QS3; P12814: ACTN1; NbExp=2; IntAct=EBI-11107474, EBI-351710; CC Q96QS3; Q9UPP1: PHF8; NbExp=3; IntAct=EBI-11107474, EBI-1560800; CC Q96QS3; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-11107474, EBI-79165; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, CC ECO:0000255|PROSITE-ProRule:PRU00138}. CC -!- TISSUE SPECIFICITY: Expressed predominantly in fetal and adult brain CC and skeletal muscle. Expression is specific to the telencephalon and CC ventral thalamus. There is an absence of expression in the cerebellum CC throughout development and also in adult. {ECO:0000269|PubMed:11889467, CC ECO:0000269|PubMed:11971879, ECO:0000269|PubMed:12359145}. CC -!- DISEASE: Lissencephaly, X-linked 2 (LISX2) [MIM:300215]: A classic type CC lissencephaly associated with abnormal genitalia. Patients have severe CC congenital or postnatal microcephaly, lissencephaly, agenesis of the CC corpus callosum, neonatal-onset intractable epilepsy, poor temperature CC regulation, chronic diarrhea, and ambiguous or underdeveloped CC genitalia. {ECO:0000269|PubMed:12379852, ECO:0000269|PubMed:14722918, CC ECO:0000269|PubMed:22194193, ECO:0000269|PubMed:31691806}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. Also called X-linked lissencephaly with abnormal genitalia CC (XLAG). {ECO:0000303|PubMed:22194193}. CC -!- DISEASE: Developmental and epileptic encephalopathy 1 (DEE1) CC [MIM:308350]: A severe form of epilepsy characterized by frequent tonic CC seizures or spasms beginning in infancy with a specific EEG finding of CC suppression-burst patterns, characterized by high-voltage bursts CC alternating with almost flat suppression phases. Patients may progress CC to West syndrome, which is characterized by tonic spasms with CC clustering, arrest of psychomotor development, and hypsarrhythmia on CC EEG. {ECO:0000269|PubMed:11889467, ECO:0000269|PubMed:12376946, CC ECO:0000269|PubMed:22194193, ECO:0000269|PubMed:27864847}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Partington syndrome (PRTS) [MIM:309510]: An X-linked CC developmental disorder characterized by intellectual disability, CC episodic dystonic hand movements, lower limb spasticity, and CC dysarthria. {ECO:0000269|PubMed:11889467}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Intellectual developmental disorder, X-linked 29 (XLID29) CC [MIM:300419]: A disorder characterized by significantly below average CC general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. CC Intellectual deficiency is the only primary symptom of non-syndromic X- CC linked forms, while syndromic intellectual disability presents with CC associated physical, neurological and/or psychiatric manifestations. CC {ECO:0000269|PubMed:11971879}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Agenesis of the corpus callosum, with abnormal genitalia CC (ACCAG) [MIM:300004]: An X-linked syndrome with variable expression in CC females. It is characterized by agenesis of corpus callosum, CC intellectual disability and seizures. Manifestations in surviving males CC include severe acquired micrencephaly, intellectual disability, limb CC contractures, scoliosis, tapered fingers with hyperconvex nails, a CC characteristic face with large eyes, prominent supraorbital ridges, CC synophrys, optic atrophy, broad alveolar ridges, and seizures. Urologic CC anomalies include renal dysplasia, cryptorchidism, and hypospadias. CC {ECO:0000269|PubMed:14722918, ECO:0000269|PubMed:22194193, CC ECO:0000269|PubMed:31691806}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the paired homeobox family. Bicoid subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY038071; AAK93901.1; -; mRNA. DR CCDS; CCDS14215.1; -. DR RefSeq; NP_620689.1; NM_139058.2. DR AlphaFoldDB; Q96QS3; -. DR SMR; Q96QS3; -. DR BioGRID; 127998; 27. DR IntAct; Q96QS3; 28. DR MINT; Q96QS3; -. DR STRING; 9606.ENSP00000368332; -. DR GlyCosmos; Q96QS3; 2 sites, 1 glycan. DR GlyGen; Q96QS3; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q96QS3; -. DR PhosphoSitePlus; Q96QS3; -. DR BioMuta; ARX; -. DR DMDM; 27923733; -. DR jPOST; Q96QS3; -. DR MassIVE; Q96QS3; -. DR PaxDb; 9606-ENSP00000368332; -. DR PeptideAtlas; Q96QS3; -. DR ProteomicsDB; 77895; -. DR Antibodypedia; 24612; 423 antibodies from 32 providers. DR DNASU; 170302; -. DR Ensembl; ENST00000379044.5; ENSP00000368332.4; ENSG00000004848.8. DR GeneID; 170302; -. DR KEGG; hsa:170302; -. DR MANE-Select; ENST00000379044.5; ENSP00000368332.4; NM_139058.3; NP_620689.1. DR UCSC; uc004dbp.5; human. DR AGR; HGNC:18060; -. DR CTD; 170302; -. DR DisGeNET; 170302; -. DR GeneCards; ARX; -. DR HGNC; HGNC:18060; ARX. DR HPA; ENSG00000004848; Group enriched (ovary, skeletal muscle). DR MalaCards; ARX; -. DR MIM; 300004; phenotype. DR MIM; 300215; phenotype. DR MIM; 300382; gene. DR MIM; 300419; phenotype. DR MIM; 308350; phenotype. DR MIM; 309510; phenotype. DR neXtProt; NX_Q96QS3; -. DR OpenTargets; ENSG00000004848; -. DR Orphanet; 2508; Corpus callosum agenesis-abnormal genitalia syndrome. DR Orphanet; 1934; Early infantile epileptic encephalopathy. DR Orphanet; 364063; Infantile epileptic-dyskinetic encephalopathy. DR Orphanet; 3451; Infantile spasms syndrome. DR Orphanet; 94083; Partington syndrome. DR Orphanet; 452; X-linked lissencephaly with abnormal genitalia. DR Orphanet; 777; X-linked non-syndromic intellectual disability. DR Orphanet; 3175; X-linked spasticity-intellectual disability-epilepsy syndrome. DR PharmGKB; PA25024; -. DR VEuPathDB; HostDB:ENSG00000004848; -. DR eggNOG; KOG0490; Eukaryota. DR GeneTree; ENSGT00940000160633; -. DR HOGENOM; CLU_047013_7_0_1; -. DR InParanoid; Q96QS3; -. DR OMA; EESCPER; -. DR OrthoDB; 3151856at2759; -. DR PhylomeDB; Q96QS3; -. DR TreeFam; TF350743; -. DR PathwayCommons; Q96QS3; -. DR SignaLink; Q96QS3; -. DR SIGNOR; Q96QS3; -. DR BioGRID-ORCS; 170302; 26 hits in 789 CRISPR screens. DR GeneWiki; Aristaless_related_homeobox; -. DR GenomeRNAi; 170302; -. DR Pharos; Q96QS3; Tbio. DR PRO; PR:Q96QS3; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q96QS3; Protein. DR Bgee; ENSG00000004848; Expressed in left ovary and 123 other cell types or tissues. DR ExpressionAtlas; Q96QS3; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0007411; P:axon guidance; IEA:Ensembl. DR GO; GO:0021846; P:cell proliferation in forebrain; IEA:Ensembl. DR GO; GO:0021853; P:cerebral cortex GABAergic interneuron migration; IEA:Ensembl. DR GO; GO:0021800; P:cerebral cortex tangential migration; IEA:Ensembl. DR GO; GO:0021831; P:embryonic olfactory bulb interneuron precursor migration; IEA:Ensembl. DR GO; GO:0072148; P:epithelial cell fate commitment; IEA:Ensembl. DR GO; GO:0021759; P:globus pallidus development; IEA:Ensembl. DR GO; GO:0044241; P:lipid digestion; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0035265; P:organ growth; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0046622; P:positive regulation of organ growth; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR003654; OAR_dom. DR PANTHER; PTHR24329; HOMEOBOX PROTEIN ARISTALESS; 1. DR PANTHER; PTHR24329:SF337; HOMEOBOX PROTEIN ARX; 1. DR Pfam; PF00046; Homeodomain; 1. DR Pfam; PF03826; OAR; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS50803; OAR; 1. DR Genevisible; Q96QS3; HS. PE 1: Evidence at protein level; KW Developmental protein; Differentiation; Disease variant; DNA-binding; KW Epilepsy; Homeobox; Intellectual disability; Lissencephaly; Neurogenesis; KW Nucleus; Reference proteome; Transcription; Transcription regulation; KW Triplet repeat expansion. FT CHAIN 1..562 FT /note="Homeobox protein ARX" FT /id="PRO_0000048819" FT DNA_BIND 328..387 FT /note="Homeobox" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 50..81 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 118..255 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 530..543 FT /note="OAR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00138" FT COMPBIAS 122..136 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 161..175 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 222..253 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 33 FT /note="L -> P (in XLID29; dbSNP:rs28936077)" FT /evidence="ECO:0000269|PubMed:11971879" FT /id="VAR_015669" FT VARIANT 115 FT /note="A -> AAAAAAAA (in DEE1)" FT /id="VAR_015177" FT VARIANT 155 FT /note="A -> AAAAAAAAA (in DEE1 and PRTS; also found in FT non-specific intellectual disability families; frequent FT variant)" FT /evidence="ECO:0000269|PubMed:11889467, FT ECO:0000269|PubMed:12376946" FT /id="VAR_015670" FT VARIANT 286 FT /note="G -> S (in XLID29; dbSNP:rs28935479)" FT /evidence="ECO:0000269|PubMed:11971879" FT /id="VAR_015671" FT VARIANT 332 FT /note="R -> H (in LISX2; dbSNP:rs111033612)" FT /evidence="ECO:0000269|PubMed:12379852, FT ECO:0000269|PubMed:14722918" FT /id="VAR_015178" FT VARIANT 332 FT /note="R -> P (in LISX2; abolishes transcriptional FT activation of KDM5C; abolishes sequence-specific FT DNA-binding; reduces transcriptional repression of LMO1 and FT SHOX2)" FT /evidence="ECO:0000269|PubMed:14722918, FT ECO:0000269|PubMed:22194193, ECO:0000269|PubMed:31691806" FT /id="VAR_033260" FT VARIANT 333 FT /note="T -> N (in ACCAG; abolishes transcriptional FT activation of KDM5C; abolishes sequence-specific FT DNA-binding; reduces transcriptional repression of LMO1 and FT SHOX2; dbSNP:rs104894745)" FT /evidence="ECO:0000269|PubMed:14722918, FT ECO:0000269|PubMed:22194193, ECO:0000269|PubMed:31691806" FT /id="VAR_033261" FT VARIANT 343 FT /note="L -> Q (in LISX2; abolishes transcriptional FT activation of KDM5C; abolishes sequence-specific FT DNA-binding; reduces transcriptional repression of LMO1 and FT SHOX2; dbSNP:rs104894741)" FT /evidence="ECO:0000269|PubMed:12379852, FT ECO:0000269|PubMed:14722918, ECO:0000269|PubMed:22194193, FT ECO:0000269|PubMed:31691806" FT /id="VAR_015179" FT VARIANT 353 FT /note="P -> L (in DEE1; corpus callosum hypoplasia and FT simplified gyral pattern observed in one patient; reduces FT sequence-specific DNA-binding; slightly reduces FT transcriptional repression of LMO1; dbSNP:rs104894743)" FT /evidence="ECO:0000269|PubMed:11889467, FT ECO:0000269|PubMed:22194193, ECO:0000269|PubMed:27864847" FT /id="VAR_015180" FT VARIANT 353 FT /note="P -> R (in LISX2; abolishes transcriptional FT activation of KDM5C; abolishes sequence-specific FT DNA-binding; reduces transcriptional repression of LMO1 and FT SHOX2)" FT /evidence="ECO:0000269|PubMed:14722918, FT ECO:0000269|PubMed:22194193, ECO:0000269|PubMed:31691806" FT /id="VAR_033262" FT VARIANT 370 FT /note="A -> V (found in a patient with a neurodevelopmental FT disorder; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35840571" FT /id="VAR_088524" FT VARIANT 521 FT /note="A -> T (in LISX2; severe phenotype; FT dbSNP:rs746120093)" FT /evidence="ECO:0000269|PubMed:14722918" FT /id="VAR_033263" FT MUTAGEN 358 FT /note="R->S: Abolishes sequence-specific DNA-binding; FT reduces transcriptional repression of LMO1 and SHOX2. FT Abolishes transcriptional activation of KDM5C." FT /evidence="ECO:0000269|PubMed:22194193, FT ECO:0000269|PubMed:31691806" FT MUTAGEN 379 FT /note="R->L,S: Abolishes sequence-specific DNA-binding; FT reduces transcriptional repression of LMO1 and SHOX2. FT Abolishes transcriptional activation of KDM5C." FT /evidence="ECO:0000269|PubMed:22194193, FT ECO:0000269|PubMed:31691806" SQ SEQUENCE 562 AA; 58160 MW; FBDF41E387C65532 CRC64; MSNQYQEEGC SERPECKSKS PTLLSSYCID SILGRRSPCK MRLLGAAQSL PAPLTSRADP EKAVQGSPKS SSAPFEAELH LPPKLRRLYG PGGGRLLQGA AAAAAAAAAA AAAAATATAG PRGEAPPPPP PTARPGERPD GAGAAAAAAA AAAAAWDTLK ISQAPQVSIS RSKSYRENGA PFVPPPPALD ELGGPGGVTH PEERLGVAGG PGSAPAAGGG TGTEDDEEEL LEDEEDEDEE EELLEDDEEE LLEDDARALL KEPRRCPVAA TGAVAAAAAA AVATEGGELS PKEELLLHPE DAEGKDGEDS VCLSAGSDSE EGLLKRKQRR YRTTFTSYQL EELERAFQKT HYPDVFTREE LAMRLDLTEA RVQVWFQNRR AKWRKREKAG AQTHPPGLPF PGPLSATHPL SPYLDASPFP PHHPALDSAW TAAAAAAAAA FPSLPPPPGS ASLPPSGAPL GLSTFLGAAV FRHPAFISPA FGRLFSTMAP LTSASTAAAL LRQPTPAVEG AVASGALADP ATAAADRRAS SIAALRLKAK EHAAQLTQLN ILPGTSTGKE VC //