CHD7

Summary

CHD7 (chromodomain helicase DNA binding protein 7, HGNC:20626) is a protein-coding gene on chromosome 8q12.2, encoding ATP-dependent chromatin remodeler CHD7 (Q9P2D1). ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55636 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CHARGE syndrome (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 41
• Clinical variants (ClinVar): 4,390 total — 622 pathogenic, 178 likely-pathogenic
• Phenotypes (HPO): 239
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_017780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20626
Approved symbol	CHD7
Name	chromodomain helicase DNA binding protein 7
Location	8q12.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1416, FLJ20357, FLJ20361
Ensembl gene	ENSG00000171316
Ensembl biotype	protein_coding
OMIM	608892
Entrez	55636

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 8 protein_coding, 8 retained_intron, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000423902, ENST00000524602, ENST00000525508, ENST00000526846, ENST00000527825, ENST00000527900, ENST00000527921, ENST00000528280, ENST00000529472, ENST00000531695, ENST00000532149, ENST00000618450, ENST00000695848, ENST00000695849, ENST00000695850, ENST00000695851, ENST00000695852, ENST00000695853, ENST00000700671, ENST00000933298, ENST00000933299, ENST00000933300

RefSeq mRNA: 2 — MANE Select: NM_017780 NM_001316690, NM_017780

CCDS: CCDS47865, CCDS83299

Canonical transcript exons

ENST00000423902 — 38 exons

Exon	Start	End
ENSE00000980480	60845250	60845409
ENSE00000980481	60848515	60848604
ENSE00000980482	60849051	60849154
ENSE00000980491	60856445	60856888
ENSE00000980492	60860904	60861125
ENSE00000980493	60862196	60862336
ENSE00001122519	60822503	60822746
ENSE00001122527	60822024	60822145
ENSE00001122533	60821790	60821927
ENSE00001122541	60820007	60820090
ENSE00001122549	60816387	60816501
ENSE00001122559	60808217	60808272
ENSE00001122564	60801528	60801593
ENSE00001137247	60823840	60824016
ENSE00001144115	60844864	60845063
ENSE00001144123	60841847	60842052
ENSE00001144130	60841644	60841754
ENSE00001144137	60838076	60838255
ENSE00001144151	60836073	60836283
ENSE00001169997	60828663	60828806
ENSE00001201866	60854363	60854523
ENSE00001201871	60852829	60853500
ENSE00001201878	60852498	60852706
ENSE00001201902	60850493	60850622
ENSE00001201934	60837668	60837835
ENSE00001201989	60800388	60800525
ENSE00001212802	60781000	60781430
ENSE00001212813	60741259	60743097
ENSE00001698705	60830322	60830577
ENSE00001790879	60836817	60837012
ENSE00002173355	60865016	60868028
ENSE00002175345	60678740	60679082
ENSE00003488217	60851262	60851319
ENSE00003516725	60851032	60851104
ENSE00003527360	60862548	60862652
ENSE00003552171	60855975	60856202
ENSE00003561610	60852019	60852247
ENSE00003571436	60794986	60795127

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.9218 / max 196.7781, expressed in 1281 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89029	2.4206	927
89030	1.2498	602
89033	1.0587	499
89031	0.9822	396
89032	0.9502	499
89037	0.6961	341
89034	0.3302	185
89028	0.1832	70
89035	0.0508	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.59	gold quality
cerebellar vermis	UBERON:0004720	97.47	gold quality
sural nerve	UBERON:0015488	97.35	gold quality
inferior vagus X ganglion	UBERON:0005363	96.38	gold quality
oocyte	CL:0000023	96.35	gold quality
lateral globus pallidus	UBERON:0002476	94.99	gold quality
ventricular zone	UBERON:0003053	94.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.38	gold quality
subthalamic nucleus	UBERON:0001906	93.96	gold quality
ventral tegmental area	UBERON:0002691	93.66	gold quality
cerebellum	UBERON:0002037	93.32	gold quality
cerebellar cortex	UBERON:0002129	93.11	gold quality
embryo	UBERON:0000922	93.06	gold quality
cerebellar hemisphere	UBERON:0002245	93.01	gold quality
pylorus	UBERON:0001166	92.68	gold quality
corpus callosum	UBERON:0002336	92.61	gold quality
ganglionic eminence	UBERON:0004023	92.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.26	gold quality
substantia nigra pars compacta	UBERON:0001965	91.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.72	gold quality
colonic epithelium	UBERON:0000397	91.61	gold quality
cardia of stomach	UBERON:0001162	91.48	gold quality
superior vestibular nucleus	UBERON:0007227	91.40	gold quality
globus pallidus	UBERON:0001875	91.38	gold quality
medulla oblongata	UBERON:0001896	91.06	gold quality
pons	UBERON:0000988	91.01	gold quality
medial globus pallidus	UBERON:0002477	90.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.59	gold quality
nipple	UBERON:0002030	90.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.40	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	36.44
E-ANND-3	yes	17.57
E-GEOD-93593	yes	9.93
E-CURD-114	yes	7.55
E-MTAB-6678	yes	4.34
E-MTAB-7303	no	354.45
E-MTAB-8060	no	185.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF4, MYB, NRG1

miRNA regulators (miRDB)

166 targeting CHD7, 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-3613-3P	100.00	76.36	7965
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-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Sequence analysis of genes located in this region detected mutations in the gene CHD7 in 10 of 17 individuals with CHARGE syndrome without microdeletions. (PMID:15300250)
• Disruption of this gene is the cause of CHARGE syndrome in twins and independently confirms the role of CHD7 in CHARGE syndrome. (PMID:16118347)
• phenotypic spectrum of developmental anomalies resulting from CHD7 dysfunction. (PMID:16169932)
• The large number human de novo mutations may be due to the combination of the Chd7 gene being a large target and the fact that many heterozygous carriers of the mutations are viable individuals with a readily detectable phenotype (PMID:16207732)
• Cardiovascular malformations, coloboma, and facial asymmetry are common findings in CHARGE syndrome caused by CHD7 mutation. (PMID:16400610)
• sequenced selected CHD7 exons in non-syndromic clefting cases from Iowa and Philippines populations, as well as matched controls. Variants in non-syndromic cases were found, however, the numbers were not statistically different from the controls. (PMID:16763960)
• Implementation of screening method for CHD7 gene and diagnosis of CHARGE syndrome. (PMID:17253929)
• We will discuss here recent aspects of the phenotypic delineation of CHARGE syndrome and highlight the role of CHD7 in its pathogeny. (PMID:17299439)
• linkage and association with 8q12 loci in idiopathic scoliosis (PMID:17436250)
• NMR analysis of the the BRK domains from CHD7 shows that each domain has a compact betabetaalphabeta fold and the second domain has a C-terminal extension consisting of two additional helices (PMID:17603073)
• these familial reports describe the intrafamilial variability of CHARGE syndrome, and underline the presence of CHD7 mutations in patients who do not fit the ‘classical clinical criteria’ for CHARGE syndrome (PMID:17661815)
• mutation detection rate of 40.5% is reflective of screening an unselected sample population referred for CHD7 testing based on suspected clinical diagnosis of CHARGE syndrome (PMID:18073582)
• Familial CHARGE syndrome and the CHD7 gene: a recurrent missense mutation, intrafamilial recurrence and variability. (PMID:18074359)
• CHD7 mutations were detected in a large proportion (64%) of cases diagnosed with CHARGE syndrome (PMID:18445044)
• exon copy number alterations of the CHD7 gene are not a major cause of CHARGE and CHARGE-like syndrome (PMID:18472328)
• R2319C mutation in the CHD7 gene is associated with ophthalmic morphologic anomalies in CHARGE syndrome (PMID:18484313)
• study describes four patients with mutations in CHD7, who had clinical features of CHARGE syndrome and who had T-B + NK + SCID (two patients) or clinical features consistent with Omenn syndrome (two patients) (PMID:18505430)
• CHD7 represents the first identified chromatin-remodeling protein with a role in human puberty and the second gene to cause both normosmic idiopathic hypogonadotropic hypogonadism and Kallmann syndrome in humans (PMID:18834967)
• A familial CHARGE syndrome with a CHD7 nonsense mutation and new clinical features. (PMID:18978652)
• CHD7 mutations can be present in Kallmann syndrome patients who have additional features that are part of the CHARGE syndrome phenotype (PMID:19021638)
• the germline mutations of the CHD7 gene and their roles in patients with congenital heart disease (CHD) (PMID:19065520)
• Clinical and genetic analysis of the CHD7 gene in Korean patients with CHARGE syndrome (PMID:19159393)
• MLPA testing is recommended in all CHARGE syndrome patients without causal CDH7 mutations. (PMID:19248844)
• Mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to defects in olfactory neural stem cell proliferation. (PMID:19279158)
• evolutionarily conserved role for CHD7 in orchestrating neural crest gene expression programs (PMID:20130577)
• CHARGE individuals with CHD7 mutations more commonly have ocular colobomas, temporal bone anomalies (semicircular canal hypoplasia/dysplasia), and facial nerve paralysis compared with mutation negative individuals. (PMID:20186815)
• This well-defined syndrome is caused by mutations in the chromodomain helicase DNA-binding (CHD7) gene, present in about 60% of CHARGE patients« (PMID:20425471)
• Disruption of the direct CHD7-CHD8 interaction might chang the conformation of a putative large complex and could be a disease mechanism in CHARGE syndrome. (PMID:20453063)
• [review] tissue-specific effects of CHD7 deficiency, known CHD7 interacting proteins, and downstream target sites for CHD7 binding; CHD7 as a critical regulator of important developmental processes in organs affected by human CHARGE syndrome (PMID:20507341)
• CHD7 functions in the nucleolus as a positive regulator of ribosomal RNA biogenesis. (PMID:20591827)
• Five novel mutations - one missense (c.2936T > C), one nonsense (c.8093C > A) and three frameshift mutations (c.804_805insAT, c.1757_1770del14, c.1793delA in patients with CHARGE syndrome (PMID:20624498)
• show that CHD7, an ATP-dependent chromatin remodeling enzyme mutated in human CHARGE syndrome, is necessary for proliferation of inner ear neuroblasts and inner ear morphogenesis. (PMID:20736290)
• in CHD7 3 novel de novo heterozygous mutations were identified:mutation in the donor splice site of intron 24, missense mutation in exon 2 and deletion in exon 11. (PMID:20943277)
• CHD7 mutations have also been found in some patients with Kallmann syndrome, hypogonadotrophic hypogonadism, and anosmia, and we discuss the overlap between this syndrome and CHARGE syndrome. (PMID:21041284)
• CHD7 mutations and CHARGE syndrome (Review) (PMID:21378379)
• De novo CHD7 mutations associated with CHARGE syndrome occur predominantly in the male germ line. (PMID:21554267)
• analysis of CHD7 mutations and clinical considerations for auditory rehabilitation in deaf patients with CHARGE syndrome (PMID:21931733)
• that bilateral large retinochoroidal colobomata represents a typical ophthalmic feature of CHARGE syndrome in patients with confirmed CHD7 mutations (PMID:22302456)
• We identified three heterozygous CHD7 mutations in patients with Kallmann syndrome. The CHD7-positive patients were carefully reexamined and were all found to have additional features of CHARGE syndrome. (PMID:22399515)
• In patients with CHARGE syndrome,the mutations are equally distributed along the coding region of CHD7 and most are nonsense or frameshift mutations. Most mutations are unique, but 94 recurrent mutations were identified. (PMID:22461308)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chd7	ENSDARG00000075211
mus_musculus	Chd7	ENSMUSG00000041235
rattus_norvegicus	Chd7	ENSRNOG00000006689

Paralogs (30): HLTF (ENSG00000071794), SMARCA2 (ENSG00000080503), SRCAP (ENSG00000080603), ATRX (ENSG00000085224), RAD54L (ENSG00000085999), BTAF1 (ENSG00000095564), CHD8 (ENSG00000100888), SMARCA1 (ENSG00000102038), CHD4 (ENSG00000111642), CHD5 (ENSG00000116254), TTF2 (ENSG00000116830), HELLS (ENSG00000119969), ZRANB3 (ENSG00000121988), CHD6 (ENSG00000124177), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

ATP-dependent chromatin remodeler CHD7 — Q9P2D1 (reviewed: Q9P2D1)

Alternative names: Chromo domain-containing protein 7

All UniProt accessions (6): A0A8Q3WKT9, A0A8V8TQJ2, Q9P2D1, E9PP20, H0YD01, H0YDC1

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP. Probable transcription regulator. May be involved in the in 45S precursor rRNA production.

Subunit / interactions. May interact with CTCF. Interacts with CHD8. Interacts with FAM124B. Found in a complex composed of AGO2, CHD7 and ARB2A. Interacts with TLK2.

Subcellular location. Nucleus Nucleus. Nucleolus.

Tissue specificity. Widely expressed in fetal and adult tissues.

Disease relevance. CHARGE syndrome (CHARGES) [MIM:214800] Common cause of congenital anomalies. Is characterized by a non-random pattern of congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina. The disease is caused by variants affecting the gene represented in this entry. Idiopathic scoliosis 3 (IS3) [MIM:608765] An abnormality of the vertebral column in which patients develop lateral curvature of the spine of at least 10 degrees. Disease susceptibility is associated with variants affecting the gene represented in this entry. Hypogonadotropic hypogonadism 5 with or without anosmia (HH5) [MIM:612370] A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be due to an intron retention. Ubiquitous, expression enriched in lung and large intestine.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9P2D1-1	1, CHD7L	yes
Q9P2D1-2	2
Q9P2D1-3	3, CHD7S
Q9P2D1-4	4

RefSeq proteins (2): NP_001303619, NP_060250* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001650	Helicase_C-like	Domain
IPR006576	BRK_domain	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR023780	Chromo_domain	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR037259	BRK_sf	Homologous_superfamily
IPR038718	SNF2-like_sf	Homologous_superfamily
IPR049730	SNF2/RAD54-like_C	Domain
IPR051493	CHD	Family
IPR056342	HTH_CHD6-9	Domain

Pfam: PF00176, PF00271, PF00385, PF07533, PF23078

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (235 total): sequence variant 143, modified residue 23, compositionally biased region 22, region of interest 11, helix 8, strand 7, sequence conflict 5, splice variant 5, domain 4, turn 3, chain 1, coiled-coil region 1, short sequence motif 1, binding site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2CKC	SOLUTION NMR
2V0E	SOLUTION NMR
2V0F	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q9P2D1 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (1): 993–1000

Post-translational modifications (23): 148, 286, 637, 725, 1577, 1581, 1874, 2231, 2233, 2237, 2251, 2272, 2275, 2356, 2395, 2472, 2533, 2535, 2551, 2559 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9943962	CHD6, CHD7, CHD8, CHD9 subfamily

MSigDB gene sets: 934 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_RIBOSOME_BIOGENESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (56): skeletal system development (GO:0001501), in utero embryonic development (GO:0001701), blood vessel remodeling (GO:0001974), heart morphogenesis (GO:0003007), ventricular trabecula myocardium morphogenesis (GO:0003222), right ventricular compact myocardium morphogenesis (GO:0003226), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), rRNA processing (GO:0006364), transcription by RNA polymerase II (GO:0006366), central nervous system development (GO:0007417), adult heart development (GO:0007512), sensory perception of sound (GO:0007605), adult walking behavior (GO:0007628), blood circulation (GO:0008015), response to bacterium (GO:0009617), regulation of gene expression (GO:0010468), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), cranial nerve development (GO:0021545), olfactory nerve development (GO:0021553), olfactory bulb development (GO:0021772), T cell differentiation (GO:0030217), female genitalia development (GO:0030540), embryonic hindlimb morphogenesis (GO:0035116), aorta morphogenesis (GO:0035909), atrioventricular canal development (GO:0036302), positive regulation of multicellular organism growth (GO:0040018), olfactory behavior (GO:0042048), inner ear morphogenesis (GO:0042472), chordate embryonic development (GO:0043009), nose development (GO:0043584), positive regulation of transcription by RNA polymerase II (GO:0045944), semicircular canal morphogenesis (GO:0048752), genitalia development (GO:0048806), regulation of neurogenesis (GO:0050767), cognition (GO:0050890), retina development in camera-type eye (GO:0060041), regulation of growth hormone secretion (GO:0060123), limb development (GO:0060173), face development (GO:0060324)

GO Molecular Function (12): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), chromatin binding (GO:0003682), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), histone binding (GO:0042393), ATP-dependent chromatin remodeler activity (GO:0140658), promoter-specific chromatin binding (GO:1990841), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
CHD chromatin remodelers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	2
heart development	2
DNA-templated transcription	2
binding	2
ATP-dependent activity	2
cellular anatomical structure	2
nuclear lumen	2
chordate embryonic development	1
tissue remodeling	1
animal organ morphogenesis	1
ventricular cardiac muscle tissue morphogenesis	1
heart trabecula morphogenesis	1
right ventricular cardiac muscle tissue morphogenesis	1
ventricular compact myocardium morphogenesis	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
nervous system development	1
sensory perception of mechanical stimulus	1
adult locomotory behavior	1
walking behavior	1
circulatory system process	1
response to other organism	1
gene expression	1
regulation of macromolecule biosynthetic process	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol	1
nerve development	1
cranial nerve development	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
DNA binding	1

Protein interactions and networks

STRING

4534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHD7	PAICS	P22234	946
CHD7	CHD8	Q9HCK8	912
CHD7	PROK2	Q9HC23	870
CHD7	PROKR2	Q8NFJ6	857
CHD7	NSMF	Q6X4W1	847
CHD7	SEMA3E	O15041	845
CHD7	ANOS1	P23352	836
CHD7	LGALS4	P56470	820
CHD7	TACR3	P29371	811
CHD7	KISS1R	Q969F8	801
CHD7	TAC3	Q9UHF0	779
CHD7	ADCY10	Q96PN6	768
CHD7	PRDM16	Q9HAZ2	762
CHD7	GNRHR	P30968	744
CHD7	SOX9	P48436	742

IntAct

96 interactions, top by confidence:

A	B	Type	Score
TLK2	DYNLL1	psi-mi:“MI:0914”(association)	0.890
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
CHD7	PARP1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
CHD7	CHD8	psi-mi:“MI:0915”(physical association)	0.510
CHD7	PBRM1	psi-mi:“MI:0915”(physical association)	0.500
CHD7	SMARCC2	psi-mi:“MI:0915”(physical association)	0.500
ETV7	NFIB	psi-mi:“MI:2364”(proximity)	0.470
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
TSG101	CHD7	psi-mi:“MI:0407”(direct interaction)	0.440
CHD8	CHD7	psi-mi:“MI:0915”(physical association)	0.370
CHD7	CHD8	psi-mi:“MI:0915”(physical association)	0.370
NES	RPL10	psi-mi:“MI:0914”(association)	0.350
CHD7	SMARCA4	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SOX2	DDX39A	psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
CBX4		psi-mi:“MI:0914”(association)	0.350
RAF1	EIF3F	psi-mi:“MI:0914”(association)	0.350
RAF1	PRPF3	psi-mi:“MI:0914”(association)	0.350

BioGRID (189): CHD7 (Affinity Capture-MS), CHD7 (Affinity Capture-MS), CHD7 (Affinity Capture-MS), WDR5 (Co-localization), ASH2L (Co-localization), RBBP5 (Co-localization), CHD8 (Co-localization), ASH2L (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), CHD7 (Affinity Capture-Western), CHD7 (Affinity Capture-Western), CHD7 (Affinity Capture-Western), CHD7 (Two-hybrid), CHD8 (Two-hybrid), CHD7 (Proximity Label-MS)

ESM2 similar proteins: A2AJK6, A2ICN5, A2VDZ3, F1LYL9, O18896, O94900, P0CB49, P34545, P46936, P46937, P48436, P49750, P55197, P61753, P61754, Q02078, Q03414, Q04887, Q06A37, Q08D57, Q2MJT0, Q3L8U1, Q3TLH4, Q571K4, Q5F3P8, Q5REW7, Q60929, Q66J90, Q66JW3, Q6F2E7, Q6KC79, Q6KCD5, Q6YXY2, Q7YRJ7, Q7ZXH3, Q8BXJ2, Q8BYH8, Q8CHI8, Q8N5C8, Q96EV2

Diamond homologs: A2A8L1, A2AJK6, A3KFM7, A7Z019, A9X4T1, B0R061, B0R0I6, B4KHL5, B5DE69, B6ZLK2, D3Z9Z9, D3ZA12, D3ZD32, E1B7X9, E7F1C4, E9PZM4, F4IHS2, F4IV45, F4IV99, F4J9M5, F4JTF6, F4JY24, F4K128, F4KBP5, F8VPZ5, G5EBZ4, G5EDG2, G5EF53, O14139, O14646, O14647, O16102, O42861, O60264, O74842, O94421, O97159, P22082, P25439, P28370

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHD7	“form complex”	SETDB1/NLK/CHD7	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 111 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
Deactivation of the beta-catenin transactivating complex	8	23.9×	6e-07
Gastrulation	6	20.0×	4e-05
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	5	19.3×	2e-04
TCF dependent signaling in response to WNT	9	13.6×	5e-06
Transcriptional regulation by RUNX1	7	13.1×	6e-05
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	13.1×	6e-05
Signaling by WNT	9	12.9×	5e-06
MITF-M-dependent gene expression	5	11.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	8	21.7×	5e-07
positive regulation of T cell differentiation	5	21.3×	2e-04
branching involved in ureteric bud morphogenesis	6	20.5×	4e-05
positive regulation of cell differentiation	7	17.5×	2e-05
somatic stem cell population maintenance	6	13.9×	3e-04
cartilage development	5	11.8×	2e-03
chromatin remodeling	17	11.6×	3e-11
transcription by RNA polymerase II	14	9.2×	6e-08

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MBL.

Clinical variants and AI predictions

ClinVar

4390 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	622
Likely pathogenic	178
Uncertain significance	1547
Likely benign	1144
Benign	258

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1032764	NM_017780.4(CHD7):c.4994G>A (p.Trp1665Ter)	Pathogenic
1032765	NM_017780.4(CHD7):c.519del (p.Pro174fs)	Pathogenic
1065461	NM_017780.4(CHD7):c.3422_3423del (p.Val1141fs)	Pathogenic
1068615	NM_017780.4(CHD7):c.6730_6733dup (p.Leu2245fs)	Pathogenic
1068670	NM_017780.4(CHD7):c.1984_1985insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCACGAGGTCAGGAGATCGAGACCATCCCGGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAACCCAAGGAGA (p.Lys662fs)	Pathogenic
1068833	NM_017780.4(CHD7):c.2195del (p.Pro732fs)	Pathogenic
1069145	NM_017780.4(CHD7):c.6641_6642del (p.Val2214fs)	Pathogenic
1069783	NM_017780.4(CHD7):c.7160C>G (p.Ser2387Ter)	Pathogenic
1069945	NM_017780.4(CHD7):c.3695_3710dup (p.Asn1237delinsLysArgTrpSerSerTer)	Pathogenic
1069987	NM_017780.4(CHD7):c.7684C>T (p.Gln2562Ter)	Pathogenic
1070565	NM_017780.4(CHD7):c.4360C>T (p.Gln1454Ter)	Pathogenic
1070672	NM_017780.4(CHD7):c.7710del (p.Val2571fs)	Pathogenic
1072854	NM_017780.4(CHD7):c.2196dup (p.Pro733fs)	Pathogenic
1072855	NM_017780.4(CHD7):c.2707_2710del (p.His903fs)	Pathogenic
1072857	NM_017780.4(CHD7):c.2957+2T>C	Pathogenic
1072858	NM_017780.4(CHD7):c.3378+5G>C	Pathogenic
1075493	NM_017780.4(CHD7):c.4906G>T (p.Glu1636Ter)	Pathogenic
1076953	NM_017780.4(CHD7):c.4888del (p.Tyr1630fs)	Pathogenic
1163023	NM_017780.4(CHD7):c.3377dup (p.Leu1126fs)	Pathogenic
1172544	NM_017780.4(CHD7):c.2239-20_2239-6del	Pathogenic
1174939	NM_017780.4(CHD7):c.4353+1G>A	Pathogenic
1181587	NM_017780.4(CHD7):c.6514G>T (p.Glu2172Ter)	Pathogenic
1185684	NM_017780.4(CHD7):c.6217C>T (p.Gln2073Ter)	Pathogenic
1185686	NM_017780.4(CHD7):c.8456del (p.Pro2819fs)	Pathogenic
1185687	NM_017780.4(CHD7):c.5912del (p.Glu1971fs)	Pathogenic
1190186	NM_017780.4(CHD7):c.7921_7922del (p.Leu2641fs)	Pathogenic
1198860	NM_017780.4(CHD7):c.2097-2A>G	Pathogenic
1203237	NM_017780.4(CHD7):c.6574G>T (p.Glu2192Ter)	Pathogenic
1299118	NM_017780.4(CHD7):c.4593G>A (p.Trp1531Ter)	Pathogenic
1301745	NM_017780.4(CHD7):c.4120_4121dup (p.Asn1374fs)	Pathogenic

SpliceAI

7817 predictions. Top by Δscore:

Variant	Effect	Δscore
8:60780996:TCA:T	acceptor_loss	1.0000
8:60780997:CAG:C	acceptor_loss	1.0000
8:60780998:A:AG	acceptor_gain	1.0000
8:60780998:AGCAT:A	acceptor_loss	1.0000
8:60780999:G:GA	acceptor_gain	1.0000
8:60780999:GC:G	acceptor_gain	1.0000
8:60780999:GCA:G	acceptor_gain	1.0000
8:60784831:GACAT:G	donor_gain	1.0000
8:60784883:GGCT:G	donor_gain	1.0000
8:60784884:G:GT	donor_gain	1.0000
8:60794984:A:AG	acceptor_gain	1.0000
8:60794985:G:GG	acceptor_gain	1.0000
8:60794985:GTA:G	acceptor_gain	1.0000
8:60800386:A:AG	acceptor_gain	1.0000
8:60800387:G:GA	acceptor_gain	1.0000
8:60800387:GA:G	acceptor_gain	1.0000
8:60800387:GAA:G	acceptor_gain	1.0000
8:60800387:GAAGA:G	acceptor_gain	1.0000
8:60800522:GCAG:G	donor_gain	1.0000
8:60800524:AGG:A	donor_loss	1.0000
8:60800526:G:GC	donor_loss	1.0000
8:60800527:T:A	donor_loss	1.0000
8:60801522:TTTTA:T	acceptor_loss	1.0000
8:60801523:TTTA:T	acceptor_loss	1.0000
8:60801526:A:AG	acceptor_gain	1.0000
8:60801527:G:GG	acceptor_gain	1.0000
8:60801527:G:GT	acceptor_loss	1.0000
8:60801527:GGA:G	acceptor_gain	1.0000
8:60808268:AACTT:A	donor_gain	1.0000
8:60808269:ACTT:A	donor_gain	1.0000

AlphaMissense

19856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:60800393:A:C	R748S	1.000
8:60800393:A:T	R748S	1.000
8:60800404:G:C	R752T	1.000
8:60800405:A:C	R752S	1.000
8:60800405:A:T	R752S	1.000
8:60800417:A:C	R756S	1.000
8:60800417:A:T	R756S	1.000
8:60816451:A:G	K855E	1.000
8:60820050:G:C	R886P	1.000
8:60821814:T:A	W908R	1.000
8:60821814:T:C	W908R	1.000
8:60822111:G:A	G975R	1.000
8:60822111:G:C	G975R	1.000
8:60822120:T:A	W978R	1.000
8:60822120:T:C	W978R	1.000
8:60822122:G:C	W978C	1.000
8:60822122:G:T	W978C	1.000
8:60822124:T:C	L979P	1.000
8:60822512:C:G	C989W	1.000
8:60822514:T:A	I990N	1.000
8:60822517:T:C	L991S	1.000
8:60822519:G:C	A992P	1.000
8:60822520:C:A	A992E	1.000
8:60822522:G:C	D993H	1.000
8:60822522:G:T	D993Y	1.000
8:60822523:A:C	D993A	1.000
8:60822523:A:T	D993V	1.000
8:60822525:G:A	E994K	1.000
8:60822526:A:T	E994V	1.000
8:60822529:T:A	M995K	1.000

dbSNP variants (sampled 300 via entrez): RS1000009717 (8:60728051 TC>T), RS1000015968 (8:60771469 T>G), RS1000037080 (8:60714613 C>T), RS1000055298 (8:60685803 C>A,T), RS1000061142 (8:60809520 T>G), RS1000076121 (8:60764522 G>A), RS1000081999 (8:60847722 A>G), RS1000090258 (8:60809180 T>C), RS1000109049 (8:60721243 A>G), RS1000121415 (8:60723460 T>C), RS1000126290 (8:60823275 T>C), RS1000126359 (8:60764180 G>A), RS1000156658 (8:60849530 A>G), RS1000161343 (8:60782454 T>A,G), RS1000171334 (8:60763989 G>T)

Disease associations

OMIM: gene MIM:608892 | disease phenotypes: MIM:612370, MIM:214800, MIM:608765, MIM:400044, MIM:219700, MIM:192350, MIM:147950, MIM:264600, MIM:213300, MIM:619681, MIM:160700, MIM:108800, MIM:608911, MIM:606215, MIM:605130, MIM:257920

GenCC curated gene-disease

Disease	Classification	Inheritance
CHARGE syndrome	Definitive	Autosomal dominant
hypogonadotropic hypogonadism 5 with or without anosmia	Strong	Autosomal dominant
Omenn syndrome	Supportive	Autosomal recessive
hypogonadotropic hypogonadism	Supportive	Autosomal dominant
Kallmann syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
CHARGE syndrome	Definitive	AD

Mondo (36): CHARGE syndrome (MONDO:0008965), hypogonadotropic hypogonadism 5 with or without anosmia (MONDO:0012880), hearing loss disorder (MONDO:0005365), neurodevelopmental disorder (MONDO:0700092), CHD7-related CHARGE syndrome (MONDO:1010178), scoliosis, isolated, susceptibility to, 3 (MONDO:0012115), 46,XY complete gonadal dysgenesis (MONDO:0010765), amenorrhea (MONDO:0001836), cleft palate (MONDO:0016064), dilated cardiomyopathy (MONDO:0005021), cystic fibrosis (MONDO:0009061), coloboma of iris (MONDO:0020356), VACTERL/vater association (MONDO:0008642), hypogonadotropic hypogonadism (MONDO:0018555), 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (MONDO:0009923)

Orphanet (23): CHARGE syndrome (Orphanet:138), Kallmann syndrome (Orphanet:478), Male infertility with spermatogenesis disorder (Orphanet:399775), 46,XY complete gonadal dysgenesis (Orphanet:242), Cleft palate (Orphanet:2014), Dilated cardiomyopathy (Orphanet:217604), Cystic fibrosis (Orphanet:586), Coloboma of iris (Orphanet:98944), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), VACTERL/VATER association (Orphanet:887), 46,XY difference of sex development due to 5-alpha-reductase 2 deficiency (Orphanet:753), Isolated Joubert syndrome (Orphanet:475), 46,XY difference of sex development (Orphanet:98085), Isolated microphthalmia-anophthalmia-coloboma (Orphanet:2542), Choanal atresia (Orphanet:137914)

HPO phenotypes

239 total (30 of 239 shown, HPO-id order):

HPO	Term
HP:0000002	Abnormality of body height
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000013	Hypoplasia of the uterus
HP:0000026	Male hypogonadism
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000048	Bifid scrotum
HP:0000050	Hypoplastic male external genitalia
HP:0000054	Micropenis
HP:0000066	Labial hypoplasia
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000089	Renal hypoplasia
HP:0000100	Nephrotic syndrome
HP:0000104	Renal agenesis
HP:0000118	Phenotypic abnormality
HP:0000126	Hydronephrosis
HP:0000134	Female hypogonadism
HP:0000144	Decreased fertility
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000275	Narrow face
HP:0000286	Epicanthus

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST001444_31	Pulmonary function decline	2.000000e-06
GCST001858_6	Refractive error	4.000000e-12
GCST004600_42	Eosinophil percentage of white cells	3.000000e-28
GCST004606_166	Eosinophil count	6.000000e-16
GCST004606_167	Eosinophil count	4.000000e-14
GCST004608_106	Granulocyte percentage of myeloid white cells	5.000000e-36
GCST004609_46	Monocyte percentage of white cells	2.000000e-24
GCST004610_165	White blood cell count	1.000000e-25
GCST004613_119	Sum neutrophil eosinophil counts	6.000000e-39
GCST004614_48	Granulocyte count	2.000000e-38
GCST004617_17	Eosinophil percentage of granulocytes	7.000000e-35
GCST004620_16	Sum basophil neutrophil counts	5.000000e-44
GCST004623_116	Neutrophil percentage of granulocytes	3.000000e-42
GCST004624_125	Sum eosinophil basophil counts	6.000000e-17
GCST004624_126	Sum eosinophil basophil counts	4.000000e-13
GCST004626_62	Myeloid white cell count	2.000000e-34
GCST004629_125	Neutrophil count	1.000000e-44
GCST004631_37	Basophil percentage of white cells	1.000000e-14
GCST004632_63	Lymphocyte percentage of white cells	2.000000e-23
GCST004633_77	Neutrophil percentage of white cells	3.000000e-44
GCST004634_59	Basophil percentage of granulocytes	3.000000e-21
GCST005312_25	Menopause (age at onset)	5.000000e-09
GCST005973_35	White blood cell count	3.000000e-13
GCST005974_1	Neutrophil count	4.000000e-14
GCST005975_16	Eosinophil count	3.000000e-08
GCST006463_12	Urinary albumin excretion (no hypertensive medication)	3.000000e-08
GCST008163_414	Height	2.000000e-06
GCST008790_32	Urinary albumin-to-creatinine ratio	6.000000e-09
GCST008794_21	Urinary albumin-to-creatinine ratio	7.000000e-09
GCST009131_15	Systemic sclerosis	4.000000e-08

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0007987	granulocyte count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007992	basophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0004704	age at menopause
EFO:0004285	albuminuria
EFO:0007778	urinary albumin to creatinine ratio

MeSH disease descriptors (24)

Descriptor	Name	Tree numbers
D000568	Amenorrhea	C23.550.568.500
D058747	CHARGE Syndrome	C09.218.458.341.186.500.250; C10.597.751.418.341.186.500.250; C10.597.751.941.162.625.250; C11.270.147.500; C11.966.075.375.250; C16.131.077.299.250; C16.320.165; C23.888.592.763.393.341.186.500.500; C23.888.592.763.941.162.625.500
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002754	Choanal Atresia	C08.460.171; C08.695.271; C09.603.171; C16.131.740.271
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
D058490	Disorder of Sex Development, 46,XY	C12.050.351.875.253.096; C12.200.706.316.096; C12.800.316.096; C16.131.939.316.096; C19.391.119.096
D017219	Gastric Outlet Obstruction	C06.405.748.340
D006061	Gonadal Dysgenesis, 46,XY	C12.050.351.875.253.096.687; C12.050.351.875.253.309.388; C12.200.706.316.096.687; C12.200.706.316.309.388; C12.800.316.096.687; C12.800.316.309.388; C16.131.939.316.096.687; C16.131.939.316.309.388; C19.391.119.096.687; C19.391.119.309.388
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D007037	Hypothyroidism	C19.874.482
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009216	Myopia	C11.744.636
D065886	Neurodevelopmental Disorders	F03.625
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D011707	Pyloric Stenosis	C06.405.748.340.690
D012600	Scoliosis	C05.116.900.800.875
C567220	Kallmann Syndrome 5 (supp.)
C535830	Pseudovaginal Perineoscrotal Hypospadias (supp.)
C536704	Wiedemann Grosse Dibbern syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lead	affects expression, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation, affects cotreatment	1
lead acetate	affects cotreatment, increases expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1

Cellosaurus cell lines

18 cell lines: 12 induced pluripotent stem cell, 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1536	NCI-H2171	Cancer cell line	Male
CVCL_B8DN	Abcam HCT 116 CHD7 KO	Cancer cell line	Male
CVCL_B9FW	Abcam A-549 CHD7 KO	Cancer cell line	Male
CVCL_C6TS	FDCHi009-A	Induced pluripotent stem cell	Male
CVCL_D2ED	Abcam MCF-7 CHD7 KO	Cancer cell line	Female
CVCL_E8SC	22Rv1 CHD7 KO clone 2A2	Cancer cell line	Male
CVCL_E8SD	22Rv1-CHD7 KO clone 1C2	Cancer cell line	Male
CVCL_LJ31	CHARGE1-11	Induced pluripotent stem cell	Male
CVCL_LJ32	CHARGE1-7	Induced pluripotent stem cell	Male
CVCL_LJ33	CHARGE2-1	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT00467870	PHASE3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism
NCT01067365	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal Treatment in Men With Secondary Hypogonadism
NCT01532414	PHASE3	COMPLETED	Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
NCT01534208	PHASE3	COMPLETED	Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01709331	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)
NCT01739582	PHASE3	COMPLETED	An Extension Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01739595	PHASE3	COMPLETED	Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism
NCT01993212	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT01993225	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT02110368	PHASE3	COMPLETED	Bioequivalence Study of Test and Reference Testosterone Topical Gel, 1.62% Metered Pump in Testosterone Deficient Adult Male Subjects Under Fasting Conditions
NCT03019575	PHASE3	COMPLETED	Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adolescent Males With Hypogonadotropic Hypogonadism (HH) (MK-8962-043)
NCT06561594	PHASE3	NOT_YET_RECRUITING	To Evaluate Recombinant Human Follicle Stimulating Hormone-CTP Fusion Protein Injection or Placebo Combined With Chorionic Gonadotropin for Injection
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00193661	PHASE2	COMPLETED	Observation Study of T-Gel (1%) in Treatment of Adolescent Boys With Hypogonadism
NCT00383656	PHASE2	UNKNOWN	Pulsatile GnRH in Anovulatory Infertility
NCT00697814	PHASE2	COMPLETED	Clomiphene in Males With Prolactinomas and Persistent Hypogonadism
NCT00706719	PHASE2	COMPLETED	To Evaluate Sperm Parameters in Men With Secondary Hypogonadism Previously Treated With Topical Testosterone
NCT00911586	PHASE2	COMPLETED	Pharmacokinetic Study to Determine Time to Steady-state
NCT01155518	PHASE2	TERMINATED	Hypogonadism in Young Men With Type 2 Diabetes
NCT01191320	PHASE2	COMPLETED	Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus