CHD6

Summary

CHD6 (chromodomain helicase DNA binding protein 6, HGNC:19057) is a protein-coding gene on chromosome 20q12, encoding ATP-dependent chromatin remodeler CHD6 (Q8TD26). ATP-dependent chromatin-remodeling factor.

This gene encodes a member of the SNF2/RAD54 helicase protein family. The encoded protein contains two chromodomains, a helicase domain, and an ATPase domain. Several multi-subunit protein complexes remodel chromatin to allow patterns of cell type-specific gene expression, and the encoded protein is thought to be a core member of one or more of these chromatin remodeling complexes. The encoded protein may function as a transcriptional repressor and is involved in the cellular repression of influenza virus replication.

Source: NCBI Gene 84181 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 354 total
• Phenotypes (HPO): 50
• MANE Select transcript: NM_032221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19057
Approved symbol	CHD6
Name	chromodomain helicase DNA binding protein 6
Location	20q12
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1335, FLJ22369, dJ620E11.1, CHD5, RIGB
Ensembl gene	ENSG00000124177
Ensembl biotype	protein_coding
OMIM	616114
Entrez	84181

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000373222, ENST00000373233, ENST00000440647, ENST00000440697, ENST00000470470, ENST00000476641, ENST00000480022, ENST00000482596, ENST00000898853

RefSeq mRNA: 1 — MANE Select: NM_032221 NM_032221

CCDS: CCDS13317

Canonical transcript exons

ENST00000373233 — 37 exons

Exon	Start	End
ENSE00000844778	41413324	41413515
ENSE00000844781	41415186	41415638
ENSE00000844783	41416588	41416794
ENSE00000844784	41417198	41417349
ENSE00000844786	41420508	41422079
ENSE00000844788	41423492	41423700
ENSE00000844789	41425178	41425394
ENSE00000844790	41426093	41426153
ENSE00000844793	41445665	41445768
ENSE00000844794	41447882	41447971
ENSE00000844795	41450946	41451105
ENSE00000844796	41451826	41452025
ENSE00000844797	41452740	41452942
ENSE00000844798	41454626	41454736
ENSE00000844799	41455800	41455979
ENSE00000844800	41457264	41457428
ENSE00000844804	41487665	41487808
ENSE00000844806	41489778	41490021
ENSE00000844807	41491698	41491819
ENSE00000844808	41493538	41493672
ENSE00000844809	41493858	41493944
ENSE00001036671	41484352	41484607
ENSE00001036699	41488428	41488604
ENSE00001355850	41437274	41437334
ENSE00001356151	41551305	41551360
ENSE00001377264	41440000	41440129
ENSE00001387501	41618340	41618377
ENSE00001459829	41402083	41405489
ENSE00001801027	41473322	41473517
ENSE00003521138	41498168	41498226
ENSE00003524038	41412144	41412263
ENSE00003532746	41514805	41514952
ENSE00003533450	41483309	41483519
ENSE00003551542	41512846	41512995
ENSE00003617641	41499295	41499357
ENSE00003687052	41533050	41533570
ENSE00003734792	41497384	41497501

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 98.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1677 / max 1162.6428, expressed in 1793 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187288	29.9124	1793
187289	0.2554	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.78	gold quality
calcaneal tendon	UBERON:0003701	96.83	gold quality
endothelial cell	CL:0000115	94.56	gold quality
adrenal tissue	UBERON:0018303	93.83	gold quality
bone marrow cell	CL:0002092	93.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.40	gold quality
colonic epithelium	UBERON:0000397	93.11	gold quality
middle temporal gyrus	UBERON:0002771	92.75	gold quality
oviduct epithelium	UBERON:0004804	92.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.59	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.20	gold quality
tendon	UBERON:0000043	90.09	gold quality
corpus callosum	UBERON:0002336	89.10	gold quality
ventricular zone	UBERON:0003053	88.64	gold quality
primary visual cortex	UBERON:0002436	87.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.65	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.36	silver quality
endometrium	UBERON:0001295	86.81	gold quality
tonsil	UBERON:0002372	86.22	gold quality
right uterine tube	UBERON:0001302	86.00	gold quality
ganglionic eminence	UBERON:0004023	85.85	gold quality
left ventricle myocardium	UBERON:0006566	85.66	silver quality
superficial temporal artery	UBERON:0001614	85.64	gold quality
thyroid gland	UBERON:0002046	85.31	gold quality
left lobe of thyroid gland	UBERON:0001120	85.21	gold quality
left ovary	UBERON:0002119	85.19	gold quality
occipital lobe	UBERON:0002021	85.16	gold quality
ovary	UBERON:0000992	85.11	gold quality
fallopian tube	UBERON:0003889	84.94	gold quality
right lobe of thyroid gland	UBERON:0001119	84.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	7.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

210 targeting CHD6, 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-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9718	99.94	68.91	918

Literature-anchored findings (GeneRIF, showing 11)

• Describes AY034072, the sequence of a gene whose original symbol, CHD5, has been changed to CHD6. (PMID:11889561)
• CHD6 colocalizes with both hypo- and hyper-phosphorlylated forms of RNA polymerase II. CHD6 was found to be present at sites of mRNA synthesis and to be part of a high molecular weight complex. (PMID:17027977)
• Both RNA knockdown experiments and mutational analyses of the E2C domain suggest that binding of CHD6 to E8–E2C contributes to the transcriptional repression of the huma papillomavirus E6/E7 oncogene promoter. (PMID:20631145)
• CHD6 has a negative role in the influenza virus cycle because the virus replicates more efficiently in CHD6-silenced cells. (PMID:21899694)
• These data indicate that CHD6 degradation is a general effect exerted by influenza A viruses and suggest that this viral repressor may play an important inhibitory role since degradation and accumulation into inactive chromatin occur during the infection. (PMID:23408615)
• CHD6 regulates the topology of the CFTR locus (PMID:25631877)
• The role of CHD6 in regulating the chromatin topology of CFTR as an exemplary genetic model for this mechanism was described. (PMID:25631877)
• Data suggest that CHD6 and CHD7 both bind with high affinity to short linker DNA, whereas CHD8 requires longer DNA for binding; thus, CHD8 slides nucleosomes into positions with more flanking linker DNA than CHD7; CHD6 disrupts nucleosomes in a distinct non-sliding manner. (PMID:28533432)
• Study shows that Chromodomain Helicase DNA-binding protein 6 (CHD6), distinct to other CHD enzymes, is stabilized during oxidative stress via reduced degradation and suggests that CHD6 is a key regulator of the oxidative DNA damage response. (PMID:30651562)
• Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology. (PMID:34021162)
• CHD6 promotes broad nucleosome eviction for transcriptional activation in prostate cancer cells. (PMID:36408932)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chd6	ENSDARG00000017244
mus_musculus	Chd6	ENSMUSG00000057133
rattus_norvegicus	Chd6	ENSRNOG00000016744

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), SMARCA4 (ENSG00000127616), INO80 (ENSG00000128908), CHD1L (ENSG00000131778), SMARCAL1 (ENSG00000138375), SHPRH (ENSG00000146414), SMARCA5 (ENSG00000153147), CHD1 (ENSG00000153922), SMARCAD1 (ENSG00000163104), RAD54L2 (ENSG00000164080), CHD3 (ENSG00000170004), CHD7 (ENSG00000171316), CHD2 (ENSG00000173575), CHD9 (ENSG00000177200), EP400 (ENSG00000183495), ERCC6L (ENSG00000186871), RAD54B (ENSG00000197275), ERCC6 (ENSG00000225830)

Protein

Protein identifiers

ATP-dependent chromatin remodeler CHD6 — Q8TD26 (reviewed: Q8TD26)

Alternative names: Chromo domain-containing protein 6, Radiation-induced gene B protein

All UniProt accessions (3): A0A075B6P4, Q8TD26, H7C294

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chromatin-remodeling factor. Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin; nucleosome disruption requires ATP. Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2. (Microbial infection) Acts as a transcriptional repressor of different viruses including influenza virus or papillomavirus. During influenza virus infection, the viral polymerase complex localizes CHD6 to inactive chromatin where it gets degraded in a proteasome independent-manner.

Subunit / interactions. Interacts with NFE2L2; involved in activation of the transcription. (Microbial infection) Interacts with the influenza A polymerase complex composed fo PB1, PB2 and PA. (Microbial infection) Interacts (via N-terminus) with human papillomavirus protein E8^E2C (via C-terminus); this interaction induces transcriptional repression of the viral genome.

Subcellular location. Nucleus. Nucleoplasm.

Tissue specificity. Widely expressed.

Disease relevance. A chromosomal aberration disrupting CHD6 has been found in a patient with mild to moderate intellectual disability and minor facial anomalies. Translocation t(18;20)(q21.1;q11.2) with TCF4 producing a CHD6-TCF4 fusion transcript.

Similarity. Belongs to the SNF2/RAD54 helicase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TD26-1	1	yes
Q8TD26-2	2
Q8TD26-3	3

RefSeq proteins (1): NP_115597* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000330	SNF2_N	Domain
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001650	Helicase_C-like	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
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, PF23078

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (50 total): compositionally biased region 12, region of interest 10, splice variant 6, domain 5, sequence conflict 5, strand 4, sequence variant 2, helix 2, chain 1, short sequence motif 1, binding site 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EPB	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q8TD26 — 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): 486–493

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9818027	NFE2L2 regulating anti-oxidant/detoxification enzymes
R-HSA-9943962	CHD6, CHD7, CHD8, CHD9 subfamily

MSigDB gene sets: 536 (showing top): CREL_01, BENPORATH_ES_WITH_H3K27ME3, WWTAAGGC_UNKNOWN, HNF3ALPHA_Q6, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, GOBP_NEUROGENESIS, GOBP_MALE_GAMETE_GENERATION, SP1_Q2_01, GOBP_FOREBRAIN_DEVELOPMENT, ATGTTAA_MIR302C, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, NKX61_01, GOBP_POSITIVE_REGULATION_OF_SIGNAL_TRANSDUCTION_BY_P53_CLASS_MEDIATOR, GOBP_CEREBRAL_CORTEX_NEURON_DIFFERENTIATION

GO Biological Process (5): chromatin remodeling (GO:0006338), regulation of gene expression (GO:0010468), cell redox homeostasis (GO:0045454), positive regulation of transcription by RNA polymerase II (GO:0045944), chromatin organization (GO:0006325)

GO Molecular Function (11): transcription coregulator binding (GO:0001221), DNA binding (GO:0003677), chromatin binding (GO:0003682), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), ATP hydrolysis activity (GO:0016887), histone binding (GO:0042393), ATP-dependent chromatin remodeler activity (GO:0140658), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nuclear events mediated by NFE2L2	1
CHD chromatin remodelers	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
ATP-dependent activity	2
cellular anatomical structure	2
chromatin organization	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cellular homeostasis	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular component organization	1
transcription factor binding	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP hydrolysis activity	1
catalytic activity, acting on DNA	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
DNA binding	1
chromatin remodeling	1
ATP-dependent activity, acting on DNA	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

2629 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHD6	NEIL1	Q96FI4	734
CHD6	CHD1	O14646	727
CHD6	ASCL1	P50553	659
CHD6	TCF4	P15884	597
CHD6	NFE2L2	Q16236	596
CHD6	NEIL2	Q969S2	594
CHD6	CHD3	Q12873	574
CHD6	BAZ1A	Q9NRL2	565
CHD6	ARID1A	O14497	562
CHD6	DPP3	Q9NY33	555
CHD6	EP300	Q09472	529
CHD6	MED16	Q9Y2X0	527
CHD6	CREBBP	Q92793	513
CHD6	MMP11	P24347	495
CHD6	PTK6	Q13882	484

IntAct

44 interactions, top by confidence:

A	B	Type	Score
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
CHD6	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
PA	CHD6	psi-mi:“MI:0915”(physical association)	0.370
CHD6	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.370
RACGAP1	STX18	psi-mi:“MI:0914”(association)	0.350
CDCA5	BDP1	psi-mi:“MI:0914”(association)	0.350
SEC16A	NCOR2	psi-mi:“MI:0914”(association)	0.350
PAPD5	UNC119B	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
Aire	NOP56	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SOX2	CBX4	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
C9orf85	MPO	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
ELK3	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
GATA2	BCL9	psi-mi:“MI:2364”(proximity)	0.270
KLF12		psi-mi:“MI:2364”(proximity)	0.270
KLF3	MCRIP1	psi-mi:“MI:2364”(proximity)	0.270
PAX6	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
PAX7	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SOX5	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
TLX2	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
TLX3	BCL9	psi-mi:“MI:2364”(proximity)	0.270
VSX1	NFIB	psi-mi:“MI:2364”(proximity)	0.270
CPSF6	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
NONO	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (86): CHD6 (Protein-peptide), CHD6 (Proximity Label-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-RNA), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-MS), CHD6 (Affinity Capture-RNA), CHD6 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9L3, A2A4P0, A2QIL2, A3KFM7, A3KMI0, B2RR83, B6ZLK2, D3ZA12, D4A2Z8, E9PZM4, F4IJV4, F4ILR7, F4JY24, F4K2E9, O14646, O14647, O18017, O42643, O45244, O60231, P24384, P34498, P40201, P93008, Q05B79, Q09530, Q10752, Q14562, Q17R09, Q38953, Q4TVV3, Q53RK8, Q54F05, Q5R746, Q5RAZ4, Q5ZI74, Q6P158, Q6P5D3, Q6PGC1, Q767K6

Diamond homologs: A0A0P0WGX7, A2A8L1, A2BGR3, A3KFM7, A6QQR4, A7Z019, A9X4T1, B0R0I6, B0XPE7, B3NAN8, B4GS98, B5BT18, B5DE69, B6ZLK2, D3Z9Z9, D3ZA12, D3ZD32, E1B7X9, F1Q8K0, F4I2H2, F4IV45, F4J9M5, F4JY24, F4K128, F4KBP5, F8VPZ5, G5EBZ4, G5EF53, O12944, O13682, O14139, O14646, O14981, O43065, O76460, P0CO16, P0CO17, P28370, P31380, P32333

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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.

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	6	8.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	264
Likely benign	28
Benign	13

Top pathogenic / likely-pathogenic (0)

SpliceAI

7493 predictions. Top by Δscore:

Variant	Effect	Δscore
20:41412142:AC:A	donor_gain	1.0000
20:41412143:CC:C	donor_gain	1.0000
20:41413317:CACT:C	donor_loss	1.0000
20:41413318:ACTT:A	donor_loss	1.0000
20:41413319:CTTA:C	donor_loss	1.0000
20:41413321:TAC:T	donor_loss	1.0000
20:41413322:A:AC	donor_gain	1.0000
20:41413322:ACT:A	donor_loss	1.0000
20:41413322:ACTG:A	donor_gain	1.0000
20:41413322:ACTGC:A	donor_gain	1.0000
20:41413323:C:CA	donor_gain	1.0000
20:41413323:CTG:C	donor_gain	1.0000
20:41413323:CTGC:C	donor_gain	1.0000
20:41413323:CTGCC:C	donor_gain	1.0000
20:41413370:AG:A	donor_gain	1.0000
20:41413512:CTTC:C	acceptor_gain	1.0000
20:41414871:AAC:A	donor_gain	1.0000
20:41416583:CTCA:C	donor_loss	1.0000
20:41416584:TCA:T	donor_loss	1.0000
20:41416585:CACCT:C	donor_loss	1.0000
20:41416586:ACC:A	donor_loss	1.0000
20:41416587:C:CT	donor_loss	1.0000
20:41416792:GTCC:G	acceptor_loss	1.0000
20:41416793:TCCT:T	acceptor_loss	1.0000
20:41416795:C:CC	acceptor_gain	1.0000
20:41416796:T:C	acceptor_loss	1.0000
20:41417232:T:A	donor_gain	1.0000
20:41417346:TAAT:T	acceptor_gain	1.0000
20:41417348:AT:A	acceptor_gain	1.0000
20:41417350:C:CC	acceptor_gain	1.0000

AlphaMissense

17995 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:41421884:A:G	L1584P	1.000
20:41421912:A:G	W1575R	1.000
20:41421912:A:T	W1575R	1.000
20:41421915:A:G	W1574R	1.000
20:41421915:A:T	W1574R	1.000
20:41423699:A:G	W1450R	1.000
20:41423699:A:T	W1450R	1.000
20:41425331:A:G	L1398P	1.000
20:41440129:C:T	G1293D	1.000
20:41445679:C:T	G1288D	1.000
20:41445680:C:G	G1288R	1.000
20:41445688:A:G	L1285P	1.000
20:41445713:A:G	W1277R	1.000
20:41445713:A:T	W1277R	1.000
20:41447939:A:G	L1239P	1.000
20:41447948:A:G	L1236P	1.000
20:41447966:A:G	L1230P	1.000
20:41447966:A:T	L1230H	1.000
20:41447971:T:A	K1228N	1.000
20:41447971:T:G	K1228N	1.000
20:41450946:T:A	K1228I	1.000
20:41450964:A:G	L1222P	1.000
20:41450964:A:T	L1222H	1.000
20:41450966:G:C	H1221Q	1.000
20:41450966:G:T	H1221Q	1.000
20:41450968:G:C	H1221D	1.000
20:41450977:A:G	Y1218H	1.000
20:41451876:A:G	L1158P	1.000
20:41451887:G:C	F1154L	1.000
20:41451887:G:T	F1154L	1.000

dbSNP variants (sampled 300 via entrez): RS1000006849 (20:41450418 A>C), RS1000007254 (20:41618149 G>C), RS1000068173 (20:41539904 T>C), RS1000075200 (20:41580140 T>C), RS1000076249 (20:41543455 C>A), RS1000081993 (20:41458102 C>T), RS1000089401 (20:41533617 T>C), RS1000101222 (20:41564315 C>T), RS1000105499 (20:41501812 T>G), RS1000128095 (20:41543713 G>A), RS1000135780 (20:41432570 C>T), RS1000139204 (20:41408412 C>T), RS1000148557 (20:41514234 G>A,C), RS1000165752 (20:41495279 A>G), RS1000165968 (20:41515813 T>C)

Disease associations

OMIM: gene MIM:616114 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000157	Abnormality of the tongue
HP:0000160	Narrow mouth
HP:0000162	Glossoptosis
HP:0000164	Abnormality of the dentition
HP:0000235	Abnormal cranial suture/fontanelle morphology
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000347	Micrognathia
HP:0000430	Underdeveloped nasal alae
HP:0000444	Convex nasal ridge
HP:0000453	Choanal atresia
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000506	Telecanthus
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0000554	Uveitis
HP:0000568	Microphthalmia
HP:0000639	Nystagmus
HP:0000653	Sparse eyelashes
HP:0000695	Natal tooth
HP:0000773	Short ribs
HP:0000821	Hypothyroidism
HP:0000896	Rib exostoses
HP:0000929	Abnormal skull morphology
HP:0001249	Intellectual disability
HP:0001321	Cerebellar hypoplasia

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001530_4	Hippocampal atrophy	8.000000e-06
GCST002701_17	Verbal declarative memory	7.000000e-06
GCST002701_18	Verbal declarative memory	7.000000e-06
GCST002990_6	Gastric adenocarcinoma (histologically verified)	7.000000e-06
GCST006614_138	Total cholesterol levels	9.000000e-09
GCST006614_30	Total cholesterol levels	1.000000e-08
GCST006661_160	Male-pattern baldness	2.000000e-15
GCST007094_235	Diastolic blood pressure	2.000000e-09
GCST007099_194	Systolic blood pressure	2.000000e-08
GCST007160_31	Refractive astigmatism	3.000000e-07
GCST008145_3	Waist circumference	8.000000e-06
GCST009391_258	Metabolite levels	6.000000e-06
GCST009391_353	Metabolite levels	9.000000e-06
GCST009391_355	Metabolite levels	5.000000e-07
GCST009391_562	Metabolite levels	3.000000e-07
GCST009391_908	Metabolite levels	1.000000e-06
GCST009391_919	Metabolite levels	3.000000e-07
GCST009441_9	Age-related cognitive decline (memory) (slope of z-scores)	8.000000e-06
GCST010173_70	Triglyceride levels	5.000000e-14
GCST010204_79	Low density lipoprotein cholesterol levels	1.000000e-21
GCST010204_8	Low density lipoprotein cholesterol levels	4.000000e-96
GCST010397_29	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-06
GCST90000025_686	Appendicular lean mass	3.000000e-12

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0005039	hippocampal atrophy
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0004574	total cholesterol measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0010426	triacylglycerol 54:8 measurement
EFO:0010433	triacylglycerol 56:6 measurement
EFO:0010434	triacylglycerol 56:7 measurement
EFO:0010498	hydroxyproline measurement
EFO:0010442	triacylglycerol 58:8 measurement
EFO:0010443	triacylglycerol 58:9 measurement
EFO:0007710	cognitive decline measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0007874	gut microbiome measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	3
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
dicrotophos	increases 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)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Decitabine	affects expression, affects methylation	1
Leflunomide	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Coumestrol	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Methotrexate	increases expression	1
Silicon Dioxide	decreases expression	1
Thiram	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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