AHDC1

Summary

AHDC1 (AT-hook DNA binding motif containing 1, HGNC:25230) is a protein-coding gene on chromosome 1p36.11-p35.3, encoding Transcription factor Gibbin (Q5TGY3). Transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome.

Source: NCBI Gene 27245 — RefSeq curated summary.

At a glance

• Gene–disease (curated): AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 1,475 total — 132 pathogenic, 45 likely-pathogenic
• Phenotypes (HPO): 199
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001371928

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25230
Approved symbol	AHDC1
Name	AT-hook DNA binding motif containing 1
Location	1p36.11-p35.3
Locus type	gene with protein product
Status	Approved
Aliases	DJ159A19.3, RP1-159A19.1
Ensembl gene	ENSG00000126705
Ensembl biotype	protein_coding
OMIM	615790
Entrez	27245

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 protein_coding, 11 protein_coding_CDS_not_defined

ENST00000247087, ENST00000374011, ENST00000480033, ENST00000487743, ENST00000490295, ENST00000642245, ENST00000642416, ENST00000643219, ENST00000643308, ENST00000644119, ENST00000644550, ENST00000644833, ENST00000644989, ENST00000645669, ENST00000646642, ENST00000646921, ENST00000673934, ENST00000868919, ENST00000868920, ENST00000868921, ENST00000868922, ENST00000931339, ENST00000931340, ENST00000931341, ENST00000954237

RefSeq mRNA: 2 — MANE Select: NM_001371928 NM_001029882, NM_001371928

CCDS: CCDS30652

Canonical transcript exons

ENST00000673934 — 9 exons

Exon	Start	End
ENSE00001462150	27547261	27552189
ENSE00001462151	27553074	27553185
ENSE00001462154	27552892	27552929
ENSE00001462157	27558706	27558883
ENSE00001462158	27603397	27603494
ENSE00001555228	27558305	27558530
ENSE00003825034	27603728	27603863
ENSE00003897127	27534245	27534916
ENSE00003898003	27604106	27604144

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2156 / max 212.4935, expressed in 1727 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11244	9.0536	1678
11245	1.3303	808
11243	0.6176	318
11240	0.2141	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	96.90	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.20	gold quality
frontal pole	UBERON:0002795	94.65	gold quality
sural nerve	UBERON:0015488	94.20	gold quality
middle frontal gyrus	UBERON:0002702	92.97	gold quality
lower esophagus mucosa	UBERON:0035834	92.79	gold quality
mucosa of stomach	UBERON:0001199	90.42	gold quality
popliteal artery	UBERON:0002250	90.31	gold quality
tibial artery	UBERON:0007610	90.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.97	gold quality
esophagus mucosa	UBERON:0002469	89.74	gold quality
skin of leg	UBERON:0001511	89.72	gold quality
cerebellar cortex	UBERON:0002129	89.67	gold quality
cerebellar hemisphere	UBERON:0002245	89.66	gold quality
cortical plate	UBERON:0005343	89.66	gold quality
ectocervix	UBERON:0012249	89.50	gold quality
body of uterus	UBERON:0009853	89.05	gold quality
right ovary	UBERON:0002118	88.95	gold quality
right adrenal gland cortex	UBERON:0035827	88.93	gold quality
decidua	UBERON:0002450	88.92	gold quality
left adrenal gland cortex	UBERON:0035825	88.85	gold quality
aorta	UBERON:0000947	88.83	gold quality
adrenal tissue	UBERON:0018303	88.82	gold quality
right adrenal gland	UBERON:0001233	88.75	gold quality
cerebellum	UBERON:0002037	88.74	gold quality
skin of abdomen	UBERON:0001416	88.68	gold quality
gastrocnemius	UBERON:0001388	88.58	gold quality
right coronary artery	UBERON:0001625	88.55	gold quality
adrenal cortex	UBERON:0001235	88.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

108 targeting AHDC1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• this study hasidentified AHDC1 de novo truncating mutations that most likely cause syndromic expressive language delay, hypotonia, and sleep apnea. (PMID:24791903)
• Microdeletion and microduplication of 1p36.11p35.3 involving AHDC1 contribute to neurodevelopmental disorder. (PMID:30615951)
• De novo heterozygous variants in AHDC1 gene were identified in two patients with partial growth hormone deficiency. (PMID:30729726)
• we unveiled that LINC01133 may function as a ceRNA for miR-4784 to advance AHDC1 expression, intensifying CC cell malignant phenotypes and EMT process, which may demonstrate the implied value of LINC01133 as a therapeutic target for CC patients. (PMID:31390932)
• Three rare mutations of AHDC1 in patients with OSA in Chinese Hanindividuals. (PMID:31737670)
• Phenotypic and protein localization heterogeneity associated with AHDC1 pathogenic protein-truncating alleles in Xia-Gibbs syndrome. (PMID:33644933)
• Phenotypic heterogeneity and mosaicism in Xia-Gibbs syndrome: Five Danish patients with novel variants in AHDC1. (PMID:34229113)
• Gibbin mesodermal regulation patterns epithelial development. (PMID:35585237)
• AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing’s sarcoma cells. (PMID:36194562)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ahdc1	ENSDARG00000093453
mus_musculus	Ahdc1	ENSMUSG00000037692
rattus_norvegicus	Ahdc1	ENSRNOG00000042855

Protein

Protein identifiers

Transcription factor Gibbin — Q5TGY3 (reviewed: Q5TGY3)

Alternative names: AT-hook DNA-binding motif-containing protein 1

All UniProt accessions (1): Q5TGY3

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis. Directly binds promoter and enhancer regions and acts by maintaining local enhancer-promoter chromatin architecture. Interacts with many sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes that wire surface ectoderm stratification.

Subcellular location. Nucleus. Chromosome.

Disease relevance. Xia-Gibbs syndrome (XIGIS) [MIM:615829] An autosomal dominant disorder characterized by intellectual disability, mild dysmorphism, hypotonia, delayed psychomotor development with absent or poor expressive language, hypoplasia of the corpus callosum, simplified gyral pattern, and delayed myelination. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_001025053, NP_001358857* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032757	DUF4683	Domain
IPR039225	AHDC1	Family

Pfam: PF15735

UniProt features (70 total): sequence variant 28, modified residue 16, region of interest 10, compositionally biased region 10, DNA-binding region 2, cross-link 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TGY3-F1	38.82	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.

Post-translational modifications (18): 79, 268, 596, 829, 846, 891, 896, 1064, 1187, 1322, 1324, 1399, 1401, 1403, 1507, 1549, 609, 1409

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 546 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MODULE_66, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_RESPONSE_TO_INSULIN, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_GASTRULATION

GO Biological Process (4): mesoderm formation (GO:0001707), cell differentiation (GO:0030154), skin morphogenesis (GO:0043589), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): DNA-binding transcription factor activity (GO:0003700), promoter-enhancer loop anchoring activity (GO:0140585), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
formation of primary germ layer	1
mesoderm morphogenesis	1
cellular developmental process	1
animal organ morphogenesis	1
skin development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
chromatin loop anchoring activity	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AHDC1	SCPEP1	Q9HB40	420
AHDC1	HUWE1	Q7Z6Z7	403
AHDC1	FBXW10B	O95170	402
AHDC1	POLD2	P49005	402
AHDC1	AGAP6	Q5VW22	380
AHDC1	KIAA0825	Q8IV33	373
AHDC1	DEDD	O75618	372
AHDC1	MED13L	Q71F56	370
AHDC1	SRCAP	Q6ZRS2	365
AHDC1	LDAF1	Q96B96	359
AHDC1	TCF20	Q9UGU0	355
AHDC1	TMEM256	Q8N2U0	348
AHDC1	CCDC28A	Q8IWP9	346
AHDC1	KDM2B	Q8NHM5	345
AHDC1	NHSL3	Q9P206	344

IntAct

61 interactions, top by confidence:

A	B	Type	Score
ATXN1	AHDC1	psi-mi:“MI:0915”(physical association)	0.670
AHDC1		psi-mi:“MI:0915”(physical association)	0.560
HTT	AHDC1	psi-mi:“MI:0915”(physical association)	0.560
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
AHDC1	TRIM68	psi-mi:“MI:0914”(association)	0.530
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
AHDC1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
AHDC1	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
AHDC1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
AHDC1	DOK5	psi-mi:“MI:0915”(physical association)	0.370
ZDHHC17	AHDC1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (104): AHDC1 (Two-hybrid), AHDC1 (Protein-peptide), AHDC1 (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), AHDC1 (Two-hybrid), AHDC1 (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS)

ESM2 similar proteins: A2VDR9, A5PKG8, A6NMT0, A7MB40, A8MUI8, E2R9X2, O00257, O15353, O43151, O55187, P19419, P30658, P48382, P52950, P59598, Q03989, Q0GGX2, Q13029, Q14781, Q28BT7, Q2MHN3, Q32MQ0, Q32N19, Q3SWY1, Q3TEI4, Q3U108, Q3UHR0, Q497V6, Q568E2, Q571I4, Q5JPB2, Q5NSW5, Q5TGY3, Q61818, Q6PAL7, Q6ZRI6, Q7TSH3, Q7Z5J4, Q811R2, Q86YN6

Diamond homologs: D3ZGX1, O48901, O60673, P14284, P90829, Q5DTT1, Q5QGS0, Q5TGY3, Q61493, Q6PAL7, Q766Z3, Q85428, Q9GSR1, Q9LVN7, Q9P6L6, P46588, Q9LRE6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
miR-4784	“up-regulates quantity by expression”	AHDC1

Disease & clinical

Clinical variants and AI predictions

ClinVar

1475 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	132
Likely pathogenic	45
Uncertain significance	596
Likely benign	487
Benign	46

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1048789	NM_001371928.1(AHDC1):c.1125dup (p.Pro376fs)	Pathogenic
1064444	NM_001371928.1(AHDC1):c.2424_2425dup (p.Gly809fs)	Pathogenic
1068817	NM_001371928.1(AHDC1):c.1346_1347del (p.Pro449fs)	Pathogenic
1164008	NM_001371928.1(AHDC1):c.1814_1819delinsT (p.Ala605fs)	Pathogenic
1320043	NM_001371928.1(AHDC1):c.1481_1482del (p.Lys494fs)	Pathogenic
133326	NM_001371928.1(AHDC1):c.2373_2374del (p.Cys791fs)	Pathogenic
133327	NM_001371928.1(AHDC1):c.2898del (p.Tyr967fs)	Pathogenic
133328	NM_001371928.1(AHDC1):c.2547del (p.Ser850fs)	Pathogenic
1341366	NM_001371928.1(AHDC1):c.2036del (p.Gly679fs)	Pathogenic
1382853	NM_001371928.1(AHDC1):c.1792C>T (p.Gln598Ter)	Pathogenic
1433194	NM_001371928.1(AHDC1):c.2111_2112dup (p.Val705fs)	Pathogenic
1455854	NM_001371928.1(AHDC1):c.257_294del (p.Pro86fs)	Pathogenic
1456392	NM_001371928.1(AHDC1):c.4442del (p.Gly1481fs)	Pathogenic
1675324	NM_001371928.1(AHDC1):c.3656G>A (p.Trp1219Ter)	Pathogenic
1685514	NM_001371928.1(AHDC1):c.2719del (p.Ala907fs)	Pathogenic
1700058	NM_001371928.1(AHDC1):c.3756del (p.Ala1253fs)	Pathogenic
1700688	NM_001371928.1(AHDC1):c.1181_1182del (p.Cys394fs)	Pathogenic
1712550	NM_001371928.1(AHDC1):c.1493T>A (p.Leu498Ter)	Pathogenic
1804100	NM_001371928.1(AHDC1):c.3182del (p.Ser1061fs)	Pathogenic
2023881	NM_001371928.1(AHDC1):c.1899_1900dup (p.Pro634fs)	Pathogenic
2024607	NM_001371928.1(AHDC1):c.3985C>T (p.Gln1329Ter)	Pathogenic
2026535	NM_001371928.1(AHDC1):c.1594dup (p.Val532fs)	Pathogenic
208156	NM_001371928.1(AHDC1):c.1881del (p.Gln627fs)	Pathogenic
208157	NM_001371928.1(AHDC1):c.3809del (p.Gln1270fs)	Pathogenic
208158	NM_001371928.1(AHDC1):c.1945del (p.Ala649fs)	Pathogenic
208159	NM_001371928.1(AHDC1):c.2529_2545del (p.Asp845fs)	Pathogenic
2120496	NM_001371928.1(AHDC1):c.3038_3047del (p.Ser1013fs)	Pathogenic
2134761	NM_001371928.1(AHDC1):c.3323G>A (p.Trp1108Ter)	Pathogenic
224806	NM_001371928.1(AHDC1):c.1402dup (p.Cys468fs)	Pathogenic
2446032	NM_001371928.1(AHDC1):c.2948del (p.Pro983fs)	Pathogenic

SpliceAI

1422 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27603392:CTCA:C	donor_loss	1.0000
1:27603393:TCACC:T	donor_loss	1.0000
1:27603394:CACCG:C	donor_loss	1.0000
1:27603395:A:AC	donor_gain	1.0000
1:27603395:ACCGG:A	donor_loss	1.0000
1:27603396:C:CC	donor_gain	1.0000
1:27603396:C:G	donor_loss	1.0000
1:27603396:CCGGA:C	donor_gain	1.0000
1:27534914:AAG:A	acceptor_gain	0.9900
1:27534916:GC:G	acceptor_loss	0.9900
1:27534917:C:CC	acceptor_gain	0.9900
1:27558700:TGTTA:T	donor_loss	0.9900
1:27558701:GTTAC:G	donor_loss	0.9900
1:27558702:TTAC:T	donor_loss	0.9900
1:27558703:TAC:T	donor_loss	0.9900
1:27558704:A:AT	donor_loss	0.9900
1:27558705:C:A	donor_loss	0.9900
1:27558879:CCCAT:C	acceptor_gain	0.9900
1:27558880:CCAT:C	acceptor_gain	0.9900
1:27558880:CCATC:C	acceptor_gain	0.9900
1:27558881:CAT:C	acceptor_gain	0.9900
1:27558881:CATC:C	acceptor_gain	0.9900
1:27558882:AT:A	acceptor_gain	0.9900
1:27558883:TC:T	acceptor_loss	0.9900
1:27558884:C:CA	acceptor_loss	0.9900
1:27558884:C:CC	acceptor_gain	0.9900
1:27558885:T:A	acceptor_loss	0.9900
1:27603395:AC:A	donor_gain	0.9900
1:27603396:CC:C	donor_gain	0.9900
1:27603396:CCGG:C	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000055063 (1:27546687 T>C), RS1000055285 (1:27560331 C>A,G,T), RS1000087396 (1:27594462 G>A), RS1000103728 (1:27601495 C>T), RS1000202963 (1:27570881 C>T), RS1000265788 (1:27595318 T>C,G), RS1000321325 (1:27556645 A>T), RS1000339865 (1:27600235 G>A), RS1000483383 (1:27564542 C>T), RS1000505870 (1:27569020 G>C), RS1000523427 (1:27552664 T>C), RS1000537270 (1:27569346 C>T), RS1000554509 (1:27562097 C>A,G,T), RS1000687781 (1:27576545 C>T), RS1000781555 (1:27562937 G>A)

Disease associations

OMIM: gene MIM:615790 | disease phenotypes: MIM:108600, MIM:615829, MIM:615812, MIM:213000

GenCC curated gene-disease

Disease	Classification	Inheritance
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome	Definitive	AD

Mondo (9): spastic ataxia (MONDO:0017845), AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome (MONDO:0014358), intellectual disability (MONDO:0001071), sleep apnea syndrome (MONDO:0005296), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092), obesity disorder (MONDO:0011122), abdominal obesity-metabolic syndrome 3 (MONDO:0014352), isolated cerebellar hypoplasia/agenesis (MONDO:0008939)

Orphanet (8): Spastic ataxia (Orphanet:316226), AHDC1-related intellectual disability-obstructive sleep apnea-mild dysmorphism syndrome (Orphanet:412069), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

199 total (30 of 199 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000154	Wide mouth
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000211	Trismus
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000234	Abnormality of the head
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000289	Broad philtrum
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000331	Short chin
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005194_60	Coronary artery disease	3.000000e-06
GCST007269_19	Pulse pressure	2.000000e-10
GCST011365_89	Myocardial infarction	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D012891	Sleep Apnea Syndromes	C08.618.085.852; C10.886.425.800.750
C562568	Cerebellar Hypoplasia (supp.)
C564815	Spastic Ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression, decreases methylation	2
sodium arsenite	decreases expression, increases methylation	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Dronabinol	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C6TD	USPi001-A	Induced pluripotent stem cell	Male
CVCL_C6TE	USPi002-A	Induced pluripotent stem cell	Male
CVCL_C6TF	USPi003-A	Induced pluripotent stem cell	Male
CVCL_D0EV	FDCHi010-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

199 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
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
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)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04297891	Not specified	UNKNOWN	Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias
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
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1