HMBOX1

Summary

HMBOX1 (homeobox containing 1, HGNC:26137) is a protein-coding gene on chromosome 8p21.1-p12, encoding Homeobox-containing protein 1 (Q6NT76). Binds directly to 5’-TTAGGG-3’ repeats in telomeric DNA.

Enables double-stranded telomeric DNA binding activity; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II; telomere maintenance via telomerase; and telomere-telomerase complex assembly. Located in several cellular components, including centrosome; chromosome, telomeric region; and nuclear body.

Source: NCBI Gene 79618 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_001135726

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26137
Approved symbol	HMBOX1
Name	homeobox containing 1
Location	8p21.1-p12
Locus type	gene with protein product
Status	Approved
Aliases	HNF1LA, PBHNF, FLJ21616, HOT1
Ensembl gene	ENSG00000147421
Ensembl biotype	protein_coding
OMIM	618610
Entrez	79618

Gene structure

Transcript identifiers

Ensembl transcripts: 74 — 67 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000287701, ENST00000355231, ENST00000397358, ENST00000517386, ENST00000518080, ENST00000519047, ENST00000519662, ENST00000521516, ENST00000522468, ENST00000523613, ENST00000524238, ENST00000558662, ENST00000560269, ENST00000560357, ENST00000560599, ENST00000561377, ENST00000887444, ENST00000887445, ENST00000887446, ENST00000887447, ENST00000887448, ENST00000887449, ENST00000887450, ENST00000887451, ENST00000887452, ENST00000887453, ENST00000887454, ENST00000887455, ENST00000887456, ENST00000887457, ENST00000887458, ENST00000887459, ENST00000887460, ENST00000887461, ENST00000887462, ENST00000887463, ENST00000887464, ENST00000887465, ENST00000887466, ENST00000887467, ENST00000887468, ENST00000887469, ENST00000887470, ENST00000887471, ENST00000887472, ENST00000887473, ENST00000887474, ENST00000887475, ENST00000887476, ENST00000887477, ENST00000887478, ENST00000887479, ENST00000887480, ENST00000887481, ENST00000887482, ENST00000887483, ENST00000887484, ENST00000887485, ENST00000887486, ENST00000887487, ENST00000887488, ENST00000887489, ENST00000887490, ENST00000887491, ENST00000887492, ENST00000887493, ENST00000966534, ENST00000966535, ENST00000966536, ENST00000966537, ENST00000966538, ENST00000966539, ENST00000966540, ENST00000966541

RefSeq mRNA: 17 — MANE Select: NM_001135726 NM_001135726, NM_001324382, NM_001324383, NM_001324384, NM_001324385, NM_001324386, NM_001324387, NM_001324388, NM_001324389, NM_001324390, NM_001324391, NM_001324392, NM_001324393, NM_001324394, NM_001324395, NM_001330498, NM_024567

CCDS: CCDS6071, CCDS83273, CCDS83274

Canonical transcript exons

ENST00000287701 — 10 exons

Exon	Start	End
ENSE00002109706	29051018	29053262
ENSE00002125770	28890395	28890678
ENSE00003620181	29048954	29049048
ENSE00003695579	28963811	28963890
ENSE00003695943	29018760	29018913
ENSE00003697472	28970043	28970519
ENSE00003699342	29047358	29047453
ENSE00003699569	29045361	29045443
ENSE00003733619	28980071	28980156
ENSE00003734410	29009072	29009182

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.7665 / max 674.6199, expressed in 1807 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88216	14.7581	1793
88220	3.5724	1268
88221	0.5677	291
88218	0.4128	190
88217	0.3708	165
88223	0.2769	136
88219	0.2221	85
205142	0.2183	104
88228	0.2033	71
88224	0.0883	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	99.36	gold quality
adrenal tissue	UBERON:0018303	96.68	gold quality
dorsal root ganglion	UBERON:0000044	96.62	gold quality
right adrenal gland cortex	UBERON:0035827	96.48	gold quality
olfactory bulb	UBERON:0002264	96.40	gold quality
right adrenal gland	UBERON:0001233	96.19	gold quality
adrenal cortex	UBERON:0001235	96.18	gold quality
secondary oocyte	CL:0000655	96.08	gold quality
cardia of stomach	UBERON:0001162	96.03	gold quality
left adrenal gland cortex	UBERON:0035825	96.01	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.92	gold quality
ventral tegmental area	UBERON:0002691	95.89	gold quality
trigeminal ganglion	UBERON:0001675	95.88	gold quality
left adrenal gland	UBERON:0001234	95.74	gold quality
corpus callosum	UBERON:0002336	95.74	gold quality
adrenal gland	UBERON:0002369	95.67	gold quality
substantia nigra pars compacta	UBERON:0001965	95.58	gold quality
medulla oblongata	UBERON:0001896	95.38	gold quality
inferior olivary complex	UBERON:0002127	95.37	gold quality
nipple	UBERON:0002030	95.33	gold quality
inferior vagus X ganglion	UBERON:0005363	95.33	gold quality
buccal mucosa cell	CL:0002336	95.21	gold quality
right lung	UBERON:0002167	95.18	gold quality
superior vestibular nucleus	UBERON:0007227	95.11	gold quality
midbrain	UBERON:0001891	94.91	gold quality
substantia nigra	UBERON:0002038	94.86	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.76	gold quality
pylorus	UBERON:0001166	94.54	gold quality
thymus	UBERON:0002370	94.52	gold quality
lateral globus pallidus	UBERON:0002476	94.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	21.36
E-ANND-3	yes	7.85

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IFNG	Repression
KLRK1
LAMP1

JASPAR motifs

Motif	Name	Family
MA0895.1	HMBOX1	POU domain factors
MA0895.2	HMBOX1	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:18585359

miRNA regulators (miRDB)

216 targeting HMBOX1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562

Literature-anchored findings (GeneRIF, showing 20)

• Hmbox1 is widely expressed in pancreas and the expression of this gene can also be detected in pallium, hippocampus and hypothalamus (PMID:16825764)
• decreased expression in hepatic carcinoma (PMID:19728927)
• These findings suggest a distinct role of HMBOX1b, and the control of mRNA splicing might be involved in homeobox genes regulation. (PMID:19757162)
• higher HMGB1(homeobox containing 1) levels in Tracheal aspirates are associated with the development of bronchopulmonary dysplasia or death in ventilated premature infants. (PMID:20182437)
• HMBOX1 negatively regulates the expression of NKG2D and the activation of the NKG2D/DAP10 signaling pathway in NK cells. (PMID:21706044)
• HMBOX1 may function as a negative regulator of IFN-gamma in NK cells. (PMID:21839858)
• our results revealed a novel regulatory mechanism: miR-30c-1(*) promoted NK cell cytotoxicity against hepatoma cells by targeting HMBOX1. (PMID:22320217)
• HOT1 supports telomerase-dependent telomere elongation. (PMID:23685356)
• a homeobox-containing protein known as HMBOX1 can directly bind telomeric double-stranded DNA and associate with PML nuclear bodies. (PMID:23813958)
• HMBOX1 regulates intracellular free zinc level by interacting with MT2A to inhibit apoptosis and promote autophagy in vascular endothelial cells. (PMID:26456220)
• Our data suggest a possible role of HMBOX1 in regulating radiosensitivity in cervical cancer cells. (PMID:28628186)
• HMBOX1 may be a potential diagnostic marker in glioma. (PMID:28731165)
• HMBOX1 played important role in the high-grade serous ovarian cancer through regulation of proliferation and apoptosis. (PMID:29709478)
• Low HMBOX1 expression is associated with liver cancer progression. (PMID:30015890)
• HMBOX1 in hepatocytes acts as a key immunosuppressive factor for inflammation (PMID:30032072)
• this study demonstrates for the first time that c-Fos/miR-18a/HMBOX1 axis plays a critical role in the progression of gliomas (PMID:30257388)
• TDD activates HMBOX1. (PMID:30358079)
• The association of HMBOX1 and CD133 with gastric neoplasm cell proliferation and migration are reported; the use of the levels of these proteins as prognostic markers are discussed. (PMID:31005794)
• Cancer-secreted exosomal miR-1468-5p promotes tumor immune escape via the immunosuppressive reprogramming of lymphatic vessels. (PMID:33388421)
• High expression of HMBOX1 promotes the progression of lung squamous cell carcinoma. (PMID:38814216)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmbox1a	ENSDARG00000027082
danio_rerio	HMBOX1	ENSDARG00000109287
mus_musculus	Hmbox1	ENSMUSG00000021972
rattus_norvegicus	Hmbox1	ENSRNOG00000013326
caenorhabditis_elegans	hmbx-1	WBGENE00018786

Protein

Protein identifiers

Homeobox-containing protein 1 — Q6NT76 (reviewed: Q6NT76)

Alternative names: Homeobox telomere-binding protein 1, Telomere-associated homeobox-containing protein 1

All UniProt accessions (6): Q6NT76, E5RGZ2, E5RHH9, H0YBM8, H0YKJ1, H0YLF2

UniProt curated annotations — full annotation on UniProt →

Function. Binds directly to 5’-TTAGGG-3’ repeats in telomeric DNA. Associates with the telomerase complex at sites of active telomere processing and positively regulates telomere elongation. Important for TERT binding to chromatin, indicating a role in recruitment of the telomerase complex to telomeres. Also plays a role in the alternative lengthening of telomeres (ALT) pathway in telomerase-negative cells where it promotes formation and/or maintenance of ALT-associated promyelocytic leukemia bodies (APBs). Enhances formation of telomere C-circles in ALT cells, suggesting a possible role in telomere recombination. Might also be involved in the DNA damage response at telomeres.

Subunit / interactions. Associates with the telomerase holoenzyme complex. Interacts with DKC1, XRCC6 and COIL.

Subcellular location. Nucleus. Cytoplasm. Chromosome. Telomere. Cajal body. PML body Nucleus.

Tissue specificity. Ubiquitous. Detected in pancreas, brain, spleen, placenta, prostate, thymus, liver, heart, bone marrow, skeletal muscle, stomach, uterus, testis, kidney, ovary, colon, lung, cardiac muscle and thyroid gland.

Domain organisation. The homeobox domain is required for binding to 5’-TTAGGG-3’ repeats in telomeres, and for telomere localization.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6NT76-1	1, HMBOX1A	yes
Q6NT76-2	2
Q6NT76-3	3
Q6NT76-4	4, HMBOX1b
Q6NT76-5	5

RefSeq proteins (17): NP_001129198, NP_001311311, NP_001311312, NP_001311313, NP_001311314, NP_001311315, NP_001311316, NP_001311317, NP_001311318, NP_001311319, NP_001311320, NP_001311321, NP_001311322, NP_001311323, NP_001311324, NP_001317427, NP_078843 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR001387	Cro/C1-type_HTH	Domain
IPR006899	HNF-1_N	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR040363	HMBOX1	Family
IPR044866	HNF_P1	Domain
IPR044869	HNF-1_POU	Domain

Pfam: PF00046, PF04814

UniProt features (39 total): cross-link 8, mutagenesis site 7, splice variant 6, compositionally biased region 4, helix 3, domain 2, modified residue 2, region of interest 2, chain 1, site 1, DNA-binding region 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4J19	X-RAY DIFFRACTION	2.9
2CUF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NT76-F1	69.43	0.39

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 (1): 335 (critical for recognition and binding of 5’-ttaggg-3’ motifs in telomeric dna)

Post-translational modifications (10): 148, 170, 60, 131, 161, 174, 217, 310, 413, 413

Mutagenesis-validated functional residues (7):

Position	Phenotype
271	abolishes binding to telomeric 5’-ttaggg-3’ motif.
325	abolishes binding to telomeric 5’-ttaggg-3’ motif.
327	impairs binding to telomeric 5’-ttaggg-3’ motif.
334	impairs binding to telomeric 5’-ttaggg-3’ motif.
335	abolishes binding to telomeric 5’-ttaggg-3’ motif. confers binding to the non-telomeric 5’-gtgagt-3’ motif.
338	impairs binding to telomeric 5’-ttaggg-3’ motif.
339	abolishes binding to telomeric 5’-ttaggg-3’ motif.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 246 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GGGACCA_MIR133A_MIR133B, GCACCTT_MIR18A_MIR18B, GOBP_CHROMOSOME_ORGANIZATION, GCM_MAP4K4, RRAGTTGT_UNKNOWN, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), telomere maintenance via telomerase (GO:0007004), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), telomere-telomerase complex assembly (GO:1905324)

GO Molecular Function (8): double-stranded telomeric DNA binding (GO:0003691), telomeric repeat DNA binding (GO:0042162), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), protein-containing complex binding (GO:0044877), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (11): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), Cajal body (GO:0015030), nuclear body (GO:0016604), PML body (GO:0016605), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA-templated transcription	2
regulation of DNA-templated transcription	2
double-stranded DNA binding	2
sequence-specific DNA binding	2
binding	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
telomerase activity	1
RNA-templated DNA biosynthetic process	1
telomere maintenance via telomere lengthening	1
telomere-telomerase complex assembly	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
telomere organization	1
protein-DNA complex assembly	1
telomeric repeat DNA binding	1
protein binding	1
DNA binding	1
nucleic acid binding	1
chromosomal region	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
nucleoplasm	1
nuclear body	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMBOX1	MT2A	P02795	576
HMBOX1	CTC1	Q2NKJ3	508
HMBOX1	HIPK1	Q86Z02	491
HMBOX1	RUVBL2	Q9Y230	481
HMBOX1	RUVBL1	P82276	480
HMBOX1	NR2E1	Q9Y466	461
HMBOX1	DMRTA2	Q96SC8	453
HMBOX1	PIH1D1	Q9NWS0	449
HMBOX1	YBX1	P16990	448
HMBOX1	NCBP1	Q09161	446
HMBOX1	ZBTB48	P10074	446
HMBOX1	NCBP2	P52298	442
HMBOX1	MYC	P01106	433
HMBOX1	SPI1	P17947	426
HMBOX1	ATRX	P46100	425

IntAct

397 interactions, top by confidence:

A	B	Type	Score
DYNLL2	HMBOX1	psi-mi:“MI:0915”(physical association)	0.800
HMBOX1	DYNLL2	psi-mi:“MI:0915”(physical association)	0.800
HMBOX1	RPL9	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	MFAP1	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	BYSL	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	FAM161A	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	AEBP2	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	ZNF417	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	KAT5	psi-mi:“MI:0915”(physical association)	0.720
SH2D4A	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
C8orf33	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
CBX8	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	ABITRAM	psi-mi:“MI:0915”(physical association)	0.720
ZNF581	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
BYSL	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
AEBP2	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
ZNF417	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	SH2D4A	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	C8orf33	psi-mi:“MI:0915”(physical association)	0.720
HMBOX1	ZNF581	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (162): HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid), HMBOX1 (Two-hybrid)

ESM2 similar proteins: A1L1C7, O08873, O42611, O60716, O94776, O94967, P83094, Q01826, Q0P5J8, Q15542, Q3UHE1, Q3UVG3, Q4R8N2, Q58A45, Q5EY87, Q5JSJ4, Q5M7R9, Q5R7S4, Q5RAR8, Q5TKA1, Q60611, Q640Q5, Q658Y4, Q68FH0, Q6ISB3, Q6NT76, Q6TEP1, Q80U28, Q8BIE6, Q8BJA3, Q8C092, Q8C0V0, Q8C735, Q8C8N2, Q8CGF6, Q8K5C0, Q8N9R8, Q8VI24, Q8WXG6, Q90ZY6

Diamond homologs: Q6NT76, Q8BJA3, Q9TYT0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HMBOX1	“down-regulates quantity by repression”	IFNG	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
Regulation of TP53 Activity	5	14.8×	3e-03
Chromatin organization	6	10.9×	3e-03
Chromatin modifying enzymes	6	9.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via homologous recombination	5	11.8×	3e-03
regulation of cell cycle	6	6.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3603 predictions. Top by Δscore:

Variant	Effect	Δscore
8:28963809:A:AG	acceptor_gain	1.0000
8:28963809:AGAAT:A	acceptor_gain	1.0000
8:28963810:G:GG	acceptor_gain	1.0000
8:28963810:GAATG:G	acceptor_gain	1.0000
8:28963886:GTGGT:G	donor_gain	1.0000
8:28970038:TTTAG:T	acceptor_loss	1.0000
8:28970039:TTAGT:T	acceptor_loss	1.0000
8:28970041:A:AG	acceptor_gain	1.0000
8:28970041:AGTTT:A	acceptor_gain	1.0000
8:28970042:G:GT	acceptor_gain	1.0000
8:28970042:GT:G	acceptor_gain	1.0000
8:28970042:GTT:G	acceptor_gain	1.0000
8:28970042:GTTT:G	acceptor_gain	1.0000
8:28970042:GTTTG:G	acceptor_gain	1.0000
8:29004026:G:GT	donor_gain	1.0000
8:29009067:CATA:C	acceptor_loss	1.0000
8:29009069:TAG:T	acceptor_loss	1.0000
8:29009181:TGGTA:T	donor_loss	1.0000
8:29009183:G:GC	donor_loss	1.0000
8:29009183:G:GG	donor_gain	1.0000
8:29009184:T:G	donor_loss	1.0000
8:29018753:A:AG	acceptor_gain	1.0000
8:29018756:TCAG:T	acceptor_loss	1.0000
8:29018758:A:AG	acceptor_gain	1.0000
8:29018758:A:C	acceptor_loss	1.0000
8:29018758:AG:A	acceptor_gain	1.0000
8:29018758:AGGC:A	acceptor_gain	1.0000
8:29018759:G:GG	acceptor_gain	1.0000
8:29018759:GG:G	acceptor_gain	1.0000
8:29018759:GGC:G	acceptor_gain	1.0000

AlphaMissense

2777 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:28970083:T:C	F22L	1.000
8:28970084:T:C	F22S	1.000
8:28970085:T:A	F22L	1.000
8:28970085:T:G	F22L	1.000
8:28970087:C:T	T23I	1.000
8:28970090:T:A	I24K	1.000
8:28970096:A:C	Q26P	1.000
8:28970099:T:A	I27K	1.000
8:28970105:T:C	L29P	1.000
8:28970108:T:A	L30H	1.000
8:28970108:T:C	L30P	1.000
8:28970108:T:G	L30R	1.000
8:28970114:G:C	R32P	1.000
8:28970117:T:A	L33H	1.000
8:28970117:T:C	L33P	1.000
8:28970120:G:C	R34P	1.000
8:28970156:C:A	A46D	1.000
8:28980092:A:C	K174N	1.000
8:28980092:A:T	K174N	1.000
8:28980100:T:A	I177N	1.000
8:28980100:T:G	I177S	1.000
8:28980104:A:C	K178N	1.000
8:28980104:A:T	K178N	1.000
8:28980108:T:A	F180I	1.000
8:28980108:T:C	F180L	1.000
8:28980109:T:C	F180S	1.000
8:28980109:T:G	F180C	1.000
8:28980110:T:A	F180L	1.000
8:28980110:T:G	F180L	1.000
8:28980112:T:A	L181H	1.000

dbSNP variants (sampled 300 via entrez): RS1000010233 (8:28915252 AT>A,ATT), RS1000010945 (8:29003753 CTTAAAT>C), RS1000014264 (8:28993341 A>G), RS1000032670 (8:28921351 A>C,G,T), RS1000048361 (8:29019659 T>C), RS1000061719 (8:29049934 G>A), RS1000079551 (8:29051270 G>A), RS1000091119 (8:28909168 A>G), RS1000112608 (8:29039740 T>A,C), RS1000146906 (8:28955230 A>G), RS1000160999 (8:28951518 AAGAC>A), RS1000172638 (8:28895657 A>G), RS1000224497 (8:28989744 T>A,C), RS1000229355 (8:28990514 A>G), RS1000240753 (8:28902893 C>T)

Disease associations

OMIM: gene MIM:618610 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_828	Obesity-related traits	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	4
Cyclosporine	increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
geraniol	increases expression	1
titanium dioxide	affects expression, increases methylation	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	decreases expression	1
NSC 689534	increases expression, affects binding	1
Temozolomide	increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1
Vehicle Emissions	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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