HMCES

Summary

HMCES (5-hydroxymethylcytosine binding, ES cell specific, HGNC:24446) is a protein-coding gene on chromosome 3q21.3, encoding Abasic site processing protein HMCES (Q96FZ2). Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites.

Enables DNA-(abasic site) binding activity; protein-DNA covalent cross-linking activity; and single-stranded DNA binding activity. Involved in interstrand cross-link repair; protein-DNA covalent cross-linking repair; and somatic hypermutation of immunoglobulin genes. Is active in replication fork.

Source: NCBI Gene 56941 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 62 total
• Druggable target: yes
• MANE Select transcript: NM_020187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24446
Approved symbol	HMCES
Name	5-hydroxymethylcytosine binding, ES cell specific
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DC12, SRAPD1
Ensembl gene	ENSG00000183624
Ensembl biotype	protein_coding
OMIM	618288
Entrez	56941

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 29 protein_coding

ENST00000383463, ENST00000389735, ENST00000417226, ENST00000502878, ENST00000509042, ENST00000509551, ENST00000510314, ENST00000511665, ENST00000857375, ENST00000857376, ENST00000857377, ENST00000857378, ENST00000857379, ENST00000857380, ENST00000857381, ENST00000857382, ENST00000857383, ENST00000857384, ENST00000857385, ENST00000857386, ENST00000857387, ENST00000857388, ENST00000857389, ENST00000928762, ENST00000928763, ENST00000928764, ENST00000949828, ENST00000949829, ENST00000949830

RefSeq mRNA: 6 — MANE Select: NM_020187 NM_001006109, NM_001363881, NM_001370343, NM_001370344, NM_001370345, NM_020187

CCDS: CCDS33852, CCDS87134

Canonical transcript exons

ENST00000383463 — 7 exons

Exon	Start	End
ENSE00001291431	129290679	129290804
ENSE00001313319	129288854	129288997
ENSE00001386444	129279710	129279915
ENSE00001497079	129301950	129302142
ENSE00001497087	129278870	129278905
ENSE00001506773	129298354	129298535
ENSE00003381974	129304589	129306186

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 94.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7138 / max 137.5056, expressed in 1767 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38516	6.6258	1720
38518	4.8930	1472
38519	0.1082	34
38517	0.0676	13
38520	0.0192	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	94.04	gold quality
gastrocnemius	UBERON:0001388	93.32	gold quality
ventricular zone	UBERON:0003053	93.26	gold quality
muscle of leg	UBERON:0001383	93.06	gold quality
ganglionic eminence	UBERON:0004023	92.98	gold quality
mucosa of transverse colon	UBERON:0004991	92.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.72	gold quality
lymph node	UBERON:0000029	92.62	gold quality
apex of heart	UBERON:0002098	92.57	gold quality
secondary oocyte	CL:0000655	92.29	gold quality
left testis	UBERON:0004533	92.27	gold quality
right testis	UBERON:0004534	92.27	gold quality
esophagus mucosa	UBERON:0002469	92.13	gold quality
mucosa of stomach	UBERON:0001199	92.03	gold quality
prefrontal cortex	UBERON:0000451	92.00	gold quality
popliteal artery	UBERON:0002250	91.84	gold quality
tibial artery	UBERON:0007610	91.83	gold quality
right atrium auricular region	UBERON:0006631	91.82	gold quality
right frontal lobe	UBERON:0002810	91.75	gold quality
nucleus accumbens	UBERON:0001882	91.68	gold quality
rectum	UBERON:0001052	91.65	gold quality
vermiform appendix	UBERON:0001154	91.50	gold quality
caudate nucleus	UBERON:0001873	91.39	gold quality
esophagus	UBERON:0001043	91.33	gold quality
putamen	UBERON:0001874	91.25	gold quality
heart left ventricle	UBERON:0002084	91.25	gold quality
cingulate cortex	UBERON:0003027	91.21	gold quality
anterior cingulate cortex	UBERON:0009835	91.13	gold quality
testis	UBERON:0000473	91.09	gold quality
descending thoracic aorta	UBERON:0002345	91.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	13.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting HMCES, 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-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-1911-5P	98.92	67.53	325
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-6834-5P	96.25	64.88	823

Literature-anchored findings (GeneRIF, showing 12)

• It involves in epigenetic changes during the progression of Alzheimer disease pathology. (PMID:24387984)
• Its reduction in brain is associate with neuropathology of Alzheimer disease. (PMID:24679604)
• The findings of this study described in this study emphasise the importance of 5hmC in brain development and ageing and will help to better understand the complexity and plasticity of the brain. (PMID:25471351)
• The expression of 5-hmC was an independent prognostic factor for overall survival of EOC [epithelial ovarian canc] patients. (PMID:25827305)
• 5-hmC might be involved in the pathogenesis of Nonalcoholic Fatty Liver Disease by regulating liver mitochondrial biogenesis and PPARGC1A expression. (PMID:26356709)
• This study reports crystal structures of the human HMCES SOS response-associated peptidase (SRAP) domain in complex with DNA-damage substrates, including HMCES cross-linked with an abasic site within a 3’ overhang DNA. (PMID:31235913)
• Characterization of global 5-hydroxymethylcytosine in pediatric posterior fossa ependymoma. (PMID:31992357)
• HMCES safeguards replication from oxidative stress and ensures error-free repair. (PMID:32307824)
• HMCES Maintains Replication Fork Progression and Prevents Double-Strand Breaks in Response to APOBEC Deamination and Abasic Site Formation. (PMID:32492421)
• Structural biology of DNA abasic site protection by SRAP proteins. (PMID:32663791)
• 5-Hydroxymethylation highlights the heterogeneity in keratinization and cell junctions in head and neck cancers. (PMID:33203436)
• Loss of the abasic site sensor HMCES is synthetic lethal with the activity of the APOBEC3A cytosine deaminase in cancer cells. (PMID:33788831)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmces	ENSDARG00000077471
mus_musculus	Hmces	ENSMUSG00000030060
rattus_norvegicus	Hmces	ENSRNOG00000079966
drosophila_melanogaster	CG11986	FBGN0037656

Protein

Protein identifiers

Abasic site processing protein HMCES — Q96FZ2 (reviewed: Q96FZ2)

Alternative names: Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein, Peptidase HMCES, SRAP domain-containing protein 1

All UniProt accessions (6): Q96FZ2, D6R9T3, D6RAI0, D6RAZ3, D6RGK7, E7EMP6

UniProt curated annotations — full annotation on UniProt →

Function. Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites. Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue. Promotes error-free repair by protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks. The HMCES DNA-protein cross-link is then either reversed or degraded. HMCES is able to catalyze the reversal of its thiazolidine cross-link and cycle between a cross-link and a non-cross-linked state depending on DNA context: mediates self-reversal of the thiazolidine cross-link in double stranded DNA, allowing APEX1 to initiate downstream repair of abasic sites. The HMCES DNA-protein cross-link can also be degraded by the SPRTN metalloprotease following unfolding by the BRIP1/FANCJ helicase. Has preference for ssDNA, but can also accommodate double-stranded DNA with 3’ or 5’ overhang (dsDNA), and dsDNA-ssDNA 3’ junction. Plays a protective role during somatic hypermutation of immunoglobulin genes in B-cells: acts via its ability to form covalent cross-links with abasic sites, thereby limiting the accumulation of deletions in somatic hypermutation target regions. Also involved in class switch recombination (CSR) in B-cells independently of the formation of a DNA-protein cross-link: acts by binding and protecting ssDNA overhangs to promote DNA double-strand break repair through the microhomology-mediated alternative-end-joining (Alt-EJ) pathway. Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine.

Subunit / interactions. Interacts (via PIP-box motif) with PCNA.

Subcellular location. Chromosome.

Post-translational modifications. Ubiquitinated; the covalent HMCES DNA-protein cross-link is ubiquitinated, leading to its degradation by the proteasome.

Activity regulation. Formation and reversal of DNA-protein cross-link depends on DNA context. Catalyzes formation of the thiazolidine linkage in presence of abasic sites in single-stranded DNA. Mediates the reversal of the thiazolidine cross-link in presence of double stranded DNA.

Domain organisation. The N-terminal catalytic Cys-2 residue forms a thiazolidine linkage to a ring-opened DNA abasic site. Glu-127 catalyzes reversal of the thiazolidine linkage; self-reversal is favoured by duplex DNA formation. Glu-127 is also involved in sensing abasic sites in single-stranded DNA (ssDNA). His-210 stabilizes the abasic sites by forming a hydrogen bond with the O4’ hydroxyl group.

Similarity. Belongs to the SOS response-associated peptidase family.

RefSeq proteins (6): NP_001006109, NP_001350810, NP_001357272, NP_001357273, NP_001357274, NP_064572* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003738	SRAP	Family
IPR036590	SRAP-like	Homologous_superfamily

Pfam: PF02586

UniProt features (59 total): strand 13, helix 12, mutagenesis site 9, cross-link 7, modified residue 4, turn 3, compositionally biased region 2, active site 2, site 2, initiator methionine 1, chain 1, region of interest 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5KO9	X-RAY DIFFRACTION	1.5
6OEA	X-RAY DIFFRACTION	2.1
6OEB	X-RAY DIFFRACTION	2.1
6OE7	X-RAY DIFFRACTION	2.2
6OOV	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FZ2-F1	82.77	0.69

Functional residue map

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

Catalytic / active sites (4): 2 (nucleophile); 127; 127 (required for sensing abasic sites); 210 (required to stabilize abasic sites)

Post-translational modifications (11): 2, 160, 295, 322, 148, 151, 275, 276, 306, 339, 342

Mutagenesis-validated functional residues (9):

Position	Phenotype
2	cells are hypersensitive to ionizing radiations. abolished ability to form a covalent cross-link with dna. does not affe
4	strongly reduced binding to single-stranded dna.
81	strongly reduced binding to single-stranded dna.
98	cells are hypersensitive to ionizing radiations. abolished ability to form a covalent cross-link with dna. abolished bin
127	abolished ability to mediate self-reversal of covalent cross-link with dna in presence of double-stranded dna.
210	decreased ability to mediate self-reversal of covalent cross-link with dna in presence of double-stranded dna.
212	abolished ability to bind dna and abolished ability to promote class switch recombination (csr) in b-cells.
337–338	abolished interaction with pcna. cells are hypersensitive to ionizing radiations.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 224 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOMF_ENDONUCLEASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_B_CELL_ACTIVATION, GOMF_NUCLEASE_ACTIVITY, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_B_CELL_MEDIATED_IMMUNITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_IMMUNOGLOBULIN_PRODUCTION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (8): proteolysis (GO:0006508), DNA damage response (GO:0006974), somatic hypermutation of immunoglobulin genes (GO:0016446), interstrand cross-link repair (GO:0036297), positive regulation of isotype switching (GO:0045830), double-strand break repair via alternative nonhomologous end joining (GO:0097681), protein-DNA covalent cross-linking repair (GO:0106300), DNA repair (GO:0006281)

GO Molecular Function (8): single-stranded DNA binding (GO:0003697), peptidase activity (GO:0008233), DNA-(abasic site) binding (GO:0140431), protein-DNA covalent cross-linking activity (GO:0160129), DNA binding (GO:0003677), protein binding (GO:0005515), hydrolase activity (GO:0016787), lyase activity (GO:0016829)

GO Cellular Component (2): replication fork (GO:0005657), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	2
catalytic activity	2
protein metabolic process	1
cellular response to stress	1
somatic diversification of immune receptors via somatic mutation	1
somatic diversification of immunoglobulins	1
positive regulation of immunoglobulin production	1
positive regulation of immunoglobulin mediated immune response	1
isotype switching	1
regulation of isotype switching	1
positive regulation of DNA recombination	1
positive regulation of B cell activation	1
positive regulation of developmental process	1
double-strand break repair via nonhomologous end joining	1
DNA metabolic process	1
DNA damage response	1
DNA binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
damaged DNA binding	1
lyase activity	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMCES	SPRTN	Q9H040	672
HMCES	RNF208	Q9H0X6	541
HMCES	STPG1	Q5TH74	507
HMCES	RFWD3	Q6PCD5	505
HMCES	TRAIP	Q9BWF2	450
HMCES	SDHAF3	Q9NRP4	447
HMCES	PRR23A	A6NEV1	445
HMCES	SMARCAL1	Q9NZC9	438
HMCES	NXT2	Q9NPJ8	431
HMCES	UNG	P13051	414
HMCES	TIPIN	Q9BVW5	401
HMCES	SSBP1	Q04837	401
HMCES	FBXO8	Q9NRD0	400
HMCES	LYSMD1	Q96S90	396
HMCES	REV1	Q9UBZ9	393

IntAct

52 interactions, top by confidence:

A	B	Type	Score
RPA4	RPA1	psi-mi:“MI:0914”(association)	0.740
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
PLK1	EVI5	psi-mi:“MI:0914”(association)	0.660
HMCES	HSPA8	psi-mi:“MI:0914”(association)	0.640
KLHDC3	DPYSL4	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
SRPK2	HMCES	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
HMCES	FAHD2A	psi-mi:“MI:0915”(physical association)	0.400
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Tipin	NEMF	psi-mi:“MI:0914”(association)	0.350
Shoc2	GABPB1	psi-mi:“MI:0914”(association)	0.350
Kifc5b	KPNA3	psi-mi:“MI:0914”(association)	0.350
Gorasp1	GOLGA2	psi-mi:“MI:0914”(association)	0.350
Nek2	WDR46	psi-mi:“MI:0914”(association)	0.350
SKA3	AP3B1	psi-mi:“MI:0914”(association)	0.350
Nfya	NFYB	psi-mi:“MI:0914”(association)	0.350
Apc	CTNNB1	psi-mi:“MI:0914”(association)	0.350
NEIL3	SF3B2	psi-mi:“MI:0914”(association)	0.350
KLHDC3	CLASP2	psi-mi:“MI:0914”(association)	0.350
RPA2	PARP1	psi-mi:“MI:0914”(association)	0.350
RPA4	PARP1	psi-mi:“MI:0914”(association)	0.350
RPA3	XRCC6	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
APOBEC3C	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350
BAG1	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Co-fractionation), HMCES (Reconstituted Complex), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS), HMCES (Affinity Capture-MS)

ESM2 similar proteins: A2VE39, A5PKL6, D2HNY3, D2HRF1, E9PYK3, F1ND48, O94952, P54276, Q1LWH4, Q2T9V5, Q4KLT3, Q4R6Y8, Q5E9N9, Q5NVR0, Q5RL51, Q5U2Z5, Q5XIJ1, Q5ZJT1, Q640B4, Q66IH9, Q68G58, Q69ZT1, Q6AYF5, Q6DCD7, Q6DDT4, Q6IND6, Q6NXW6, Q6P7N4, Q7SXA9, Q7TPQ3, Q8BYH3, Q8CE96, Q8K4M9, Q8N1G2, Q8NEC7, Q8R1M0, Q8VDH1, Q91XL9, Q96FZ2, Q99575

Diamond homologs: O31916, O34906, O34915, O64131, Q5NVR0, Q5XIJ1, Q5ZJT1, Q6IND6, Q6P7N4, Q8R1M0, Q96FZ2, Q04471

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Dual Incision in GG-NER	5	27.0×	2e-04
Formation of Incision Complex in GG-NER	5	26.4×	2e-04
Regulation of HSF1-mediated heat shock response	7	20.3×	2e-05
B-WICH complex positively regulates rRNA expression	5	12.7×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
base-excision repair	5	38.4×	1e-04
nucleotide-excision repair	5	31.4×	2e-04
telomere maintenance	5	21.9×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1178 predictions. Top by Δscore:

Variant	Effect	Δscore
3:129288993:TTAAG:T	donor_loss	1.0000
3:129288994:TAAG:T	donor_loss	1.0000
3:129288995:AAG:A	donor_loss	1.0000
3:129288996:AG:A	donor_loss	1.0000
3:129288997:GG:G	donor_loss	1.0000
3:129288998:G:A	donor_loss	1.0000
3:129288999:T:A	donor_loss	1.0000
3:129298351:CA:C	acceptor_loss	1.0000
3:129298353:GTC:G	acceptor_gain	1.0000
3:129298353:GTCA:G	acceptor_gain	1.0000
3:129298514:GCT:G	donor_gain	1.0000
3:129305473:T:A	acceptor_gain	1.0000
3:129279839:A:G	donor_gain	0.9900
3:129288850:GCAG:G	acceptor_loss	0.9900
3:129288851:CAG:C	acceptor_loss	0.9900
3:129288852:A:T	acceptor_loss	0.9900
3:129298352:A:AG	acceptor_gain	0.9900
3:129298353:G:GT	acceptor_gain	0.9900
3:129298353:GT:G	acceptor_gain	0.9900
3:129298531:CACAG:C	donor_loss	0.9900
3:129298532:ACAGG:A	donor_loss	0.9900
3:129298533:CAGGC:C	donor_loss	0.9900
3:129298534:AGGCA:A	donor_loss	0.9900
3:129298535:GGCA:G	donor_loss	0.9900
3:129298536:G:T	donor_loss	0.9900
3:129298537:CAA:C	donor_loss	0.9900
3:129301461:G:GT	donor_gain	0.9900
3:129301910:T:G	acceptor_gain	0.9900
3:129301910:T:TA	acceptor_gain	0.9900
3:129302139:AAAGG:A	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000572 (3:129299963 T>A,C), RS1000055403 (3:129292258 T>C), RS1000093345 (3:129299661 T>C), RS1000251625 (3:129293988 T>C), RS1000315681 (3:129284063 C>T), RS1000424381 (3:129287159 C>T), RS1000458643 (3:129287369 G>A,T), RS1000762704 (3:129288579 C>A), RS1001230187 (3:129284772 C>T), RS1001246679 (3:129306550 C>A,G,T), RS1001301649 (3:129278145 T>C), RS1001522846 (3:129295351 C>A,T), RS1001605543 (3:129284481 TGTC>T), RS1001670596 (3:129301712 G>A), RS1001763569 (3:129301223 A>T)

Disease associations

OMIM: gene MIM:618288 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005956_82	Waist-to-hip ratio adjusted for BMI	2.000000e-07
GCST005958_5	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-10
GCST005962_16	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-11
GCST012227_1004	Hip circumference adjusted for BMI	9.000000e-17
GCST012227_1255	Hip circumference adjusted for BMI	3.000000e-09
GCST90020028_1836	Hip circumference adjusted for BMI	2.000000e-10
GCST90020028_1838	Hip circumference adjusted for BMI	7.000000e-11
GCST90020028_1839	Hip circumference adjusted for BMI	3.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724664 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
N(4)-hydroxycytidine	increases expression	1
beta-lapachone	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	decreases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Vorinostat	increases expression	1
Panobinostat	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Bleomycin	decreases expression	1
Cisplatin	increases expression	1
Fluorouracil	affects response to substance	1
Lead	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697337	Binding	Inhibition of C3ORF37 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1ZA	HAP1 HMCES (-) 1	Cancer cell line	Male
CVCL_E1ZB	HAP1 HMCES (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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