ZNF711

Summary

ZNF711 (ZFX family zinc finger ZNF711, HGNC:13128) is a protein-coding gene on chromosome Xq21.1, encoding Zinc finger protein 711 (Q9Y462). Transcription regulator required for brain development.

This gene encodes a zinc finger protein of unknown function. It bears similarity to a zinc finger protein which acts as a transcriptional activator. This gene lies in a region of the X chromosome which has been associated with cognitive disability.

Source: NCBI Gene 7552 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 287 total — 6 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 13
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001330574

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13128
Approved symbol	ZNF711
Name	ZFX family zinc finger ZNF711
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	CMPX1, ZNF4, ZNF5, dJ75N13.1, Zfp711, MRX97
Ensembl gene	ENSG00000147180
Ensembl biotype	protein_coding
OMIM	314990
Entrez	7552

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 32 protein_coding

ENST00000276123, ENST00000360700, ENST00000373165, ENST00000674551, ENST00000881748, ENST00000881749, ENST00000881750, ENST00000881751, ENST00000881752, ENST00000881753, ENST00000881754, ENST00000881755, ENST00000881756, ENST00000881757, ENST00000881758, ENST00000881759, ENST00000881760, ENST00000939577, ENST00000939578, ENST00000939579, ENST00000939580, ENST00000939581, ENST00000939582, ENST00000939583, ENST00000939584, ENST00000939585, ENST00000939586, ENST00000939587, ENST00000939588, ENST00000972099, ENST00000972100, ENST00000972101

RefSeq mRNA: 9 — MANE Select: NM_001330574 NM_001330574, NM_001375431, NM_001375432, NM_001375433, NM_001375434, NM_001375435, NM_001375436, NM_001375437, NM_021998

CCDS: CCDS35344, CCDS83481

Canonical transcript exons

ENST00000674551 — 11 exons

Exon	Start	End
ENSE00000979138	85264275	85264430
ENSE00000979139	85265118	85265255
ENSE00000979141	85270003	85270146
ENSE00000979143	85255259	85255801
ENSE00001018777	85245903	85246022
ENSE00001018778	85247547	85247651
ENSE00001459688	85268294	85268341
ENSE00001521616	85267278	85267415
ENSE00003900690	85243991	85244191
ENSE00003901432	85270651	85273357
ENSE00003904164	85246930	85247188

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 97.40.

FANTOM5 (CAGE): breadth broad, TPM avg 9.8594 / max 541.3629, expressed in 893 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196843	5.4541	639
196845	3.1486	642
196844	0.7448	392
196842	0.2451	128
196841	0.1793	88
196846	0.0875	23

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.40	gold quality
cortical plate	UBERON:0005343	96.97	gold quality
ganglionic eminence	UBERON:0004023	96.56	gold quality
ventricular zone	UBERON:0003053	96.17	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.82	gold quality
adrenal tissue	UBERON:0018303	92.70	gold quality
right testis	UBERON:0004534	91.19	gold quality
tibia	UBERON:0000979	90.71	gold quality
left testis	UBERON:0004533	89.51	gold quality
testis	UBERON:0000473	88.88	gold quality
primary visual cortex	UBERON:0002436	88.31	gold quality
middle temporal gyrus	UBERON:0002771	87.96	gold quality
embryo	UBERON:0000922	87.22	gold quality
right adrenal gland cortex	UBERON:0035827	86.33	gold quality
right adrenal gland	UBERON:0001233	85.83	gold quality
entorhinal cortex	UBERON:0002728	85.04	gold quality
adrenal cortex	UBERON:0001235	84.64	gold quality
occipital lobe	UBERON:0002021	84.34	gold quality
adrenal gland	UBERON:0002369	84.16	gold quality
left adrenal gland cortex	UBERON:0035825	83.77	gold quality
left adrenal gland	UBERON:0001234	83.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.21	gold quality
superior frontal gyrus	UBERON:0002661	83.18	gold quality
postcentral gyrus	UBERON:0002581	82.59	gold quality
prefrontal cortex	UBERON:0000451	82.31	gold quality
endometrium	UBERON:0001295	82.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.19	gold quality
germinal epithelium of ovary	UBERON:0001304	81.64	gold quality
temporal lobe	UBERON:0001871	81.53	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
KDM5C	Activation

miRNA regulators (miRDB)

197 targeting ZNF711, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-25-3P	99.98	74.60	1817

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation is reported. (PMID:20346720)
• A total of six novel and 11 known single nucleotide polymorphisms were identified. Further studies are warranted to analyze the candidate genes at Xq11.1-q21.33. (PMID:21384559)
• The KCTD5/cullin3 complex stabilizes ZNF711 transcription factor. (PMID:26188516)
• Two large four-generation families have been described with a total of 11 males affected with intellectual disability (ID) caused by mutations in ZNF711, all present with mild to moderate ID and poor speech accompanied by autistic features and mild facial dysmorphisms, suggesting that ZNF711mutations cause non-syndromic ID. (PMID:27993705)
• Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters. (PMID:32406922)
• Analysis of a Set of KDM5C Regulatory Genes Mutated in Neurodevelopmental Disorders Identifies Temporal Coexpression Brain Signatures. (PMID:34356104)
• ZNF711 down-regulation promotes CISPLATIN resistance in epithelial ovarian cancer via interacting with JHDM2A and suppressing SLC31A1 expression. (PMID:34521054)
• Clinical findings and a DNA methylation signature in kindreds with alterations in ZNF711. (PMID:34992252)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf711	ENSDARG00000071868
mus_musculus	Zfp711	ENSMUSG00000025529
rattus_norvegicus	Zfp711	ENSRNOG00000022391

Paralogs (38): ZFX (ENSG00000005889), ZBTB11 (ENSG00000066422), ZFAT (ENSG00000066827), ZFY (ENSG00000067646), ZNF586 (ENSG00000083828), IKZF5 (ENSG00000095574), ZNF419 (ENSG00000105136), ZNF549 (ENSG00000121406), ZSCAN20 (ENSG00000121903), ZNF304 (ENSG00000131845), PRDM15 (ENSG00000141956), ZNF660 (ENSG00000144792), ZNF773 (ENSG00000152439), ZNF256 (ENSG00000152454), ZNF837 (ENSG00000152475), ZNF691 (ENSG00000164011), ZNF610 (ENSG00000167554), E4F1 (ENSG00000167967), ZNF562 (ENSG00000171466), ZNF561 (ENSG00000171469), ZNF584 (ENSG00000171574), ZIK1 (ENSG00000171649), ZNF570 (ENSG00000171827), ZSCAN2 (ENSG00000176371), ZNF552 (ENSG00000178935), ZNF154 (ENSG00000179909), ZNF792 (ENSG00000180884), ZNF793 (ENSG00000188227), ZNF548 (ENSG00000188785), ZNF79 (ENSG00000196152), ZNF418 (ENSG00000196724), ZNF772 (ENSG00000197128), ZNF583 (ENSG00000198440), ZNF480 (ENSG00000198464), ZNF551 (ENSG00000204519), ZNF134 (ENSG00000213762), ZNF587B (ENSG00000269343), ZNF8 (ENSG00000278129)

Protein

Protein identifiers

Zinc finger protein 711 — Q9Y462 (reviewed: Q9Y462)

Alternative names: Zinc finger protein 6

All UniProt accessions (1): Q9Y462

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator required for brain development. Probably acts as a transcription factor that binds to the promoter of target genes and recruits PHF8 histone demethylase, leading to activated expression of genes involved in neuron development, such as KDM5C. May compete with transcription factor ARX for activation of expression of KDM5C.

Subunit / interactions. Interacts with PHF8.

Subcellular location. Nucleus.

Tissue specificity. Expressed in neural tissues.

Disease relevance. Intellectual developmental disorder, X-linked 97 (XLID97) [MIM:300803] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The sixth zinc finger contains a Phe residue, Phe-584, instead of the final His residue normally found in C2H2-type zinc fingers. There is another His residue a few residues downstream, His-587, but this is not involved in coordinating zinc. Despite the His to Phe substitution, the zinc finger retains the ability to bind zinc using a tridentate metal-binding site of Cys-564, Cys-567 and His-580. The zinc finger also has hydrolytic activity against 4-nitrophenyl acetate.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y462-1	1	yes
Q9Y462-2	2
Q9Y462-3	3

RefSeq proteins (9): NP_001317503, NP_001362360, NP_001362361, NP_001362362, NP_001362363, NP_001362364, NP_001362365, NP_001362366, NP_068838 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006794	Transcrp_activ_Zfx/Zfy-dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050826	Krueppel_C2H2_ZnFinger	Family

Pfam: PF00096, PF04704

UniProt features (43 total): zinc finger region 12, sequence conflict 10, sequence variant 7, binding site 3, cross-link 3, splice variant 2, mutagenesis site 2, chain 1, region of interest 1, turn 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9CJA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y462-F1	55.68	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 564; 567; 580

Post-translational modifications (3): 224, 235, 296

Mutagenesis-validated functional residues (2):

Position	Phenotype
584	site can coordinate zn(2+); when associated with a-587.
587	does not affect binding of the protein to zn(2+) alone or when associated with h-584.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 237 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, TGCACTT_MIR519C_MIR519B_MIR519A, TATTATA_MIR374, ATGCAGT_MIR217, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, CREB_Q4, AGTCTTA_MIR499, SOX9_B1, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, E4F1_Q6, RICKMAN_HEAD_AND_NECK_CANCER_A, ATF4_Q2, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, YY1_01

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), regulation of gene expression (GO:0010468), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
gene expression	1
regulation of macromolecule biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transition metal ion binding	1
DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF711	POF1B	Q8WVV4	643
ZNF711	PHF8	Q9UPP1	627
ZNF711	SATL1	Q86VE3	601
ZNF711	ZNF3	P13683	575
ZNF711	APOOL	Q6UXV4	569
ZNF711	ZNF7	P17015	530
ZNF711	BRWD3	Q6RI45	508
ZNF711	UBE2D1	P51668	498
ZNF711	TEX13B	Q9BXU2	493
ZNF711	TEX13A	Q9BXU3	488
ZNF711	ZUP1	Q96AP4	447
ZNF711	ATRX	P46100	429
ZNF711	DIAPH2	O60879	420
ZNF711	PCED1A	Q9H1Q7	418
ZNF711	ZC3H14	Q6PJT7	416

IntAct

30 interactions, top by confidence:

A	B	Type	Score
PHF8	ZNF711	psi-mi:“MI:0915”(physical association)	0.690
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
	ZNF711	psi-mi:“MI:0915”(physical association)	0.370
CCL22	ZNF711	psi-mi:“MI:0915”(physical association)	0.370
CCL24	ZNF711	psi-mi:“MI:0915”(physical association)	0.370
IFNA1	ZNF711	psi-mi:“MI:0915”(physical association)	0.370
IL3	ZNF711	psi-mi:“MI:0915”(physical association)	0.370
IL31	ZNF711	psi-mi:“MI:0915”(physical association)	0.370
LTA	ZNF711	psi-mi:“MI:0915”(physical association)	0.370
rl3_rl3l_human	NKRF	psi-mi:“MI:0914”(association)	0.350
RPS19	ZNF320	psi-mi:“MI:0914”(association)	0.350
YBX2		psi-mi:“MI:0914”(association)	0.350
KRR1	PES1	psi-mi:“MI:0914”(association)	0.350
RPL23A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
AIM2	DDX39A	psi-mi:“MI:0914”(association)	0.350
PYHIN1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
MNDA	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
fumA	ZNF711	psi-mi:“MI:0915”(physical association)	0.000
ZNF711	OPTN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): ZNF711 (Proximity Label-MS), ZNF711 (Two-hybrid), ZNF711 (Affinity Capture-Western), KCTD5 (Affinity Capture-Western), CUL3 (Affinity Capture-Western), ZNF711 (Affinity Capture-MS), ZNF711 (Proximity Label-MS), ZNF711 (Affinity Capture-MS), ZNF711 (Two-hybrid), ZNF711 (Affinity Capture-MS), ZNF711 (Affinity Capture-MS), ZNF711 (Affinity Capture-MS), ZNF711 (Affinity Capture-MS), ZNF711 (Affinity Capture-MS), ZNF711 (Affinity Capture-MS)

ESM2 similar proteins: A1L1J6, A2ANX9, A7Y7X5, E9Q8T2, G5E8B9, O15060, O43167, O43829, O62836, O95625, P08048, P0C6P6, P10925, P17010, P17012, P20662, P52739, Q01611, Q08376, Q0VCB0, Q2FAY8, Q3TTC2, Q4V8R6, Q52V16, Q5DU09, Q5PPG4, Q5R5M1, Q5R5N5, Q5RAU9, Q5SVQ8, Q6B4Z5, Q6GNP2, Q6INV8, Q7TS63, Q7ZVR6, Q80V63, Q80X44, Q811F1, Q8K3J5, Q92010

Diamond homologs: A0A9P4XV22, A2ANX9, B1H2Q6, O62836, P08048, P0CJ78, P10925, P17010, P17012, P20662, P27705, P28698, P52288, P80944, Q01611, Q03081, Q03125, Q0VDT2, Q29419, Q3U3I9, Q52V16, Q567C6, Q5U2Z0, Q6B4Z5, Q7RTV3, Q95LI3, Q966L8, Q96EG3, Q9UDV6, Q9UL36, Q9Y462, A1L2U9, A2A884, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, O35615, O77459

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Major pathway of rRNA processing in the nucleolus and cytosol	5	16.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
immune response	5	10.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

287 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	9
Uncertain significance	139
Likely benign	19
Benign	19

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1028742	NM_001330574.2(ZNF711):c.1068_1069del (p.Arg356fs)	Pathogenic
3259325	NM_001330574.2(ZNF711):c.1199_1203del (p.Gln400fs)	Pathogenic
3259326	NM_001330574.2(ZNF711):c.531_532dup (p.Gly178fs)	Pathogenic
417761	NM_001330574.2(ZNF711):c.2192del (p.Phe731fs)	Pathogenic
9762	NM_001330574.2(ZNF711):c.2265_2266del (p.Cys755_Glu756delinsTer)	Pathogenic
9763	NM_001330574.2(ZNF711):c.1711A>T (p.Arg571Ter)	Pathogenic
2430809	NM_001330574.2(ZNF711):c.2299C>T (p.Arg767Ter)	Likely pathogenic
2499146	NM_001330574.2(ZNF711):c.1681C>T (p.Arg561Ter)	Likely pathogenic
2921256	NM_001330574.2(ZNF711):c.2217del (p.Lys739fs)	Likely pathogenic
3384374	NM_001330574.2(ZNF711):c.1495C>T (p.Arg499Ter)	Likely pathogenic
4076363	NM_001330574.2(ZNF711):c.1243del (p.Thr415fs)	Likely pathogenic
417762	NM_001330574.2(ZNF711):c.731T>C (p.Ile244Thr)	Likely pathogenic
4211813	NM_001330574.2(ZNF711):c.2217dup (p.His740fs)	Likely pathogenic
4689791	NM_001330574.2(ZNF711):c.2218del (p.His740fs)	Likely pathogenic
495110	NM_001330574.2(ZNF711):c.1377dup (p.Tyr460fs)	Likely pathogenic

SpliceAI

1532 predictions. Top by Δscore:

Variant	Effect	Δscore
X:85244188:GCAG:G	donor_gain	1.0000
X:85244192:G:GA	donor_loss	1.0000
X:85244192:G:GG	donor_gain	1.0000
X:85255257:A:AG	acceptor_gain	1.0000
X:85255258:G:GG	acceptor_gain	1.0000
X:85255258:GT:G	acceptor_gain	1.0000
X:85255797:ATCTT:A	donor_gain	1.0000
X:85255798:TCTT:T	donor_gain	1.0000
X:85255802:G:GG	donor_gain	1.0000
X:85264265:T:G	acceptor_gain	1.0000
X:85264266:A:AG	acceptor_gain	1.0000
X:85264267:T:G	acceptor_gain	1.0000
X:85264270:TATAG:T	acceptor_loss	1.0000
X:85264271:A:AG	acceptor_gain	1.0000
X:85264271:ATAGT:A	acceptor_gain	1.0000
X:85264272:T:G	acceptor_gain	1.0000
X:85264273:A:AG	acceptor_gain	1.0000
X:85264273:AGT:A	acceptor_gain	1.0000
X:85264273:AGTG:A	acceptor_gain	1.0000
X:85264274:G:GG	acceptor_gain	1.0000
X:85264274:GT:G	acceptor_gain	1.0000
X:85264274:GTG:G	acceptor_gain	1.0000
X:85264274:GTGG:G	acceptor_gain	1.0000
X:85264274:GTGGA:G	acceptor_gain	1.0000
X:85264372:TTCTG:T	donor_gain	1.0000
X:85264427:A:AG	donor_gain	1.0000
X:85264427:A:G	donor_gain	1.0000
X:85264429:AGGTA:A	donor_loss	1.0000
X:85264431:GTAC:G	donor_loss	1.0000
X:85265113:TTAA:T	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000366451 (X:85266021 C>G), RS1000682712 (X:85253781 A>C), RS1000740839 (X:85263974 T>C), RS1000807306 (X:85269637 G>C), RS1000936956 (X:85245149 C>A,T), RS1000977941 (X:85257321 C>G), RS1001041714 (X:85258386 G>A), RS1001146716 (X:85244569 C>T), RS1001325206 (X:85257729 C>A), RS1001398730 (X:85272236 G>C), RS1001514880 (X:85272701 G>A), RS1001589822 (X:85261556 T>C), RS1001703418 (X:85264796 C>G), RS1001756518 (X:85252196 A>C), RS1001868161 (X:85242480 T>C)

Disease associations

OMIM: gene MIM:314990 | disease phenotypes: MIM:300803, MIM:601665

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 97	Definitive	X-linked
non-syndromic X-linked intellectual disability	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Definitive	XL

Mondo (4): intellectual disability, X-linked 97 (MONDO:0010430), inherited obesity (MONDO:0019182), intellectual disability (MONDO:0001071), non-syndromic X-linked intellectual disability (MONDO:0019181)

Orphanet (3): X-linked non-syndromic intellectual disability (Orphanet:777), Genetic obesity (Orphanet:77828), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000276	Long face
HP:0000283	Broad face
HP:0000400	Macrotia
HP:0000664	Synophrys
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001270	Motor delay
HP:0001417	X-linked inheritance
HP:0001513	Obesity
HP:0002342	Moderate intellectual disability
HP:0011220	Prominent forehead
HP:0011463	Childhood onset

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)
C567583	Mental Retardation, X-Linked, Znf711-Related (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	6
sodium arsenite	increases expression, decreases expression, increases abundance	4
Benzo(a)pyrene	decreases expression, affects methylation	3
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
potassium chromate(VI)	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Chromium	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Methotrexate	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Silver	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

207 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT05093634	PHASE3	ACTIVE_NOT_RECRUITING	EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
NCT07220772	PHASE3	RECRUITING	A Study Evaluating Mibavademab Treatment of Obesity Due to Leptin (LEP) Gene Mutations in Children, Adolescents and Adults
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT03013543	PHASE2	COMPLETED	Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity
NCT04963231	PHASE2	COMPLETED	DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04710056	Not specified	AVAILABLE	Expanded Access to REGN4461 for Patients With Diseases Associated With Deficient Leptin Signaling
NCT05362565	Not specified	UNKNOWN	Genetic Research of Monogenic Obesity in a Pediatric Cohort With Severe and Early Onset Obesity
NCT06113523	Not specified	UNKNOWN	Genetic Research of Monogenic Obesity in a Pediatric Cohort With Severe and Early Onset Obesity (GENOBE)
NCT06380426	Not specified	RECRUITING	Real-life Evaluation of WEGOVY (Semaglutide) Treatment in Adults With Monogenic Obesity (ObGeSema)
NCT07296900	Not specified	RECRUITING	International Genetic Obesity Registry
NCT07302802	Not specified	RECRUITING	Efficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome