OLFM4

Summary

OLFM4 (olfactomedin 4, HGNC:17190) is a protein-coding gene on chromosome 13q14.3, encoding Olfactomedin-4 (Q6UX06). May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase.

This gene was originally cloned from human myeloblasts and found to be selectively expressed in inflammed colonic epithelium. This gene encodes a member of the olfactomedin family. The encoded protein is an antiapoptotic factor that promotes tumor growth and is an extracellular matrix glycoprotein that facilitates cell adhesion.

Source: NCBI Gene 10562 — RefSeq curated summary.

At a glance

• GWAS associations: 42
• Clinical variants (ClinVar): 76 total — 1 pathogenic
• MANE Select transcript: NM_006418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17190
Approved symbol	OLFM4
Name	olfactomedin 4
Location	13q14.3
Locus type	gene with protein product
Status	Approved
Aliases	OlfD, GW112, GC1, pDP4
Ensembl gene	ENSG00000102837
Ensembl biotype	protein_coding
OMIM	614061
Entrez	10562

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000219022

RefSeq mRNA: 1 — MANE Select: NM_006418 NM_006418

CCDS: CCDS9440

Canonical transcript exons

ENST00000219022 — 5 exons

Exon	Start	End
ENSE00000683303	53043105	53043264
ENSE00000923604	53028813	53029040
ENSE00000939604	53041910	53042122
ENSE00001315467	53049969	53052057
ENSE00003550900	53034348	53034500

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 99.87.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 8.4342 / max 2850.6614, expressed in 91 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135247	8.2640	90
135246	0.1635	24
135248	0.0067	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	99.87	gold quality
jejunal mucosa	UBERON:0000399	99.79	gold quality
duodenum	UBERON:0002114	99.55	gold quality
ileal mucosa	UBERON:0000331	99.44	gold quality
ileum	UBERON:0002116	99.33	silver quality
type B pancreatic cell	CL:0000169	98.84	gold quality
rectum	UBERON:0001052	98.61	gold quality
caecum	UBERON:0001153	98.11	gold quality
vermiform appendix	UBERON:0001154	97.93	gold quality
islet of Langerhans	UBERON:0000006	97.88	gold quality
mucosa of transverse colon	UBERON:0004991	97.40	gold quality
bone marrow	UBERON:0002371	96.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.66	gold quality
trabecular bone tissue	UBERON:0002483	95.51	gold quality
small intestine	UBERON:0002108	94.78	gold quality
bone marrow cell	CL:0002092	94.42	gold quality
epithelial cell of pancreas	CL:0000083	93.76	gold quality
pancreas	UBERON:0001264	93.55	gold quality
body of pancreas	UBERON:0001150	92.88	gold quality
palpebral conjunctiva	UBERON:0001812	92.12	gold quality
colonic mucosa	UBERON:0000317	91.22	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.24	gold quality
transverse colon	UBERON:0001157	87.53	gold quality
oocyte	CL:0000023	86.67	gold quality
vagina	UBERON:0000996	85.79	gold quality
caput epididymis	UBERON:0004358	85.04	gold quality
secondary oocyte	CL:0000655	84.90	gold quality
gall bladder	UBERON:0002110	82.86	gold quality
intestine	UBERON:0000160	82.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	5974.31
E-CURD-46	yes	2829.83
E-CURD-7	yes	646.93
E-ENAD-21	yes	646.93
E-MTAB-9801	yes	6.60
E-HCAD-31	yes	4.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2C, NFKB1, NFKB, NFKBIA, RARA, RELA

miRNA regulators (miRDB)

83 targeting OLFM4, 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-4533	100.00	69.48	2758
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6745	99.74	65.33	1321

Literature-anchored findings (GeneRIF, showing 40)

• Data show that granulocyte colony stimulating factor stimulated clone-1, an extracellular matrix glycoprotein, facilitates cell adhesion. (PMID:16566923)
• The expression pattern of hGC-1 protein in 173 cases of gastric carcinoma was investigated and a striking correlation was demonstrated between hGC-1 expression and histological type and differentiation of gastric carcinoma. (PMID:17650212)
• hGC-1 may be a useful marker for tumor differentiation and progression of human colon carcinoma. (PMID:18281536)
• We generated human monoclonal antibodies against 2 potential tumor targets, NGAL and GW112, and we proved their selective expression in cancer colon and not or barely in healthy tissues. (PMID:18798264)
• OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. (PMID:19450592)
• High serum olfactomedin 4 is associated with gastric cancer. (PMID:19670418)
• OLFM4 plays an important role in myeloid leukemia cellular functions (PMID:20724538)
• Review critically evaluates recent advances in understanding of the transcriptional regulation of OLFM4 and its upstream signalling pathways with special emphasis on carcinogenesis and outline future perspectives in the field (PMID:20878207)
• Results show that cross-talk between estrogen and EGF signaling regulates OLFM-4 expression in human endometrium. (PMID:21048224)
• OLFM4 expression and its biological significances in tumor differentiation and progression as well as the contributions of OLFM4 to tumorigenesis (Review) (PMID:21067260)
• Olfactomedin 4 expression has been associated with progression of cervical intraepithelial neoplasia and differentiation of cervical cancer. (PMID:21270618)
• miR-486 antioncogenic activity may involve the direct targeting and inhibition of OLFM4. (PMID:21415212)
• protection of AGT and resistance to nitrosamine-induced genotoxicity critically depends on GSNOR in hepatocytes (PMID:21470957)
• The expression of OLFM4 mRNA or protein differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph node metastases. (PMID:21904905)
• Our results also indicate that OLFM4 is regulated by the Ras-NF-kappaB2 pathway, one of the main oncogenic pathways deregulated in colorectal tumors (PMID:21986994)
• Results suggest that S100B, TM4SF3, and OLFM4 overexpression may affect metastatic behavior of tumor cells in Taiwanese colorectal cancer patients. (PMID:22011044)
• OLFM4 identifies a subset of human neutrophils. (PMID:22187488)
• OLFM4 is overexpressed in active IBD and secreted into mucus. OLFM4 seems to be of functional relevance in IBD as a mucus component, possibly by binding defensins. (PMID:22398066)
• depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H2O2 or TNF alpha treatment by increasing caspase-3 dependent apoptosis. (PMID:22471589)
• Single nucleotide polymorphism in OLFM4 gene is associated with childhood obesity. (PMID:22484627)
• OLFM4 regulates host defense against a broad range of bacteria including Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli in an OLFM4-deficient mouse model. (PMID:22844115)
• Reduced expression of olfactomedin 4 and ectopic expression of claudin-18 might be useful markers in the differential diagnosis of serrated polyps. (PMID:23570326)
• OLFM4 is a novel candidate tumor-suppressor gene for chromosome 13q and may shed new light on strategies that could be used for the diagnosis, prognosis, and treatment of prostate cancer patients. (PMID:24070418)
• Impairment of ERalpha signal-mediated OLFM4 expression promoted the malignant progression of endometrioid adenocarcinoma. (PMID:24495253)
• Using a human vaginal epithelial cell line, the expression of mucin 5 subtype B and olfactomedin-4 were down-regulated in response to N9, suggesting these markers could apply to humans (PMID:25333937)
• OLM4 expression is increased in the early stages of gastric, colorectal, and pancreatic cancer initiation. (PMID:25400027)
• although low OLFM4 expression is not an independent prognostic biomarker, it might indicate worse prognosis for smoking patients with non-small cell lung cancer (PMID:25771901)
• High expression of GW112 in colorectal cancer tissues and reduced expression of GRIM-19 in colorectal cancer tissues may be associated with abnormal proliferation of cancer cells. (PMID:26011333)
• findings suggest that OLFM4 is not only involved in early stages of gastric carcinogenesis but also a useful prognostic marker for advanced gastric cancer (PMID:26070873)
• Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. (PMID:26162090)
• Study demonstrates that epigenetic silencing of OLFM4 enhances gastric cancer cell invasion via activation of FAK signaling. (PMID:26303970)
• suppression of OLFM4 expression may be a promising strategy in the development of novel cancer therapeutic drugs (PMID:26398045)
• Data show that olfactomedin 4 (OLFM4) is highly expressed in proliferating benign epithelial cells and in some carcinoma cells. (PMID:26416558)
• olfactomedin 4 appears to play a critical role in regulating progression of prostate cancer, and has potential as a new biomarker for prostate cancer. (PMID:26581960)
• OLFM4 is downregulated by miR-486-5p, which contributes to ovarian cancer tumorigenesis. Conversely, estrogen receptor signaling downregulates miR-486-5p and upregulates OLFM4 expression, slowing the development and progression of ovarian cancer. (PMID:26871282)
• OLFM4 has an important role in the regulation of intestinal inflammation and tumorigenesis, and could be a potential therapeutic target for intestinal malignant tumors. Unlike the human colonic epithelium, the mouse colonic epithelium does not express OLFM4, but nevertheless, systemic OLFM4 deletion promotes colon tumorigenesis and that loss from mucosal neutrophils may have a role to play. (PMID:26973250)
• Olfactomedin-4 identifies a subpopulation of neutrophils in patients with septic shock, and those with a high percentage of olfactomedin-4+ neutrophils are at higher risk for greater organ failure burden and death. Olfactomedin-4 might serve as a marker of a pathogenic neutrophil subset in patients with septic shock (PMID:27635771)
• Olfactomedin 4 is a novel tumor marker for triple-negative breast cancer for predicting and prognosis. (PMID:27939521)
• OLFM4 is proved to as a functional target for miR-590. (PMID:28012926)
• MiR-103 acts as an oncogene miRNA to promote triple-negative breast cancer cells migration and invasion through targeting OLFM4. (PMID:28320108)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	olfm4.2	ENSDARG00000041960
danio_rerio	olfm4.1	ENSDARG00000087625
mus_musculus	Olfm4	ENSMUSG00000022026
rattus_norvegicus	Olfm4	ENSRNOG00000013280

Paralogs (9): MYOC (ENSG00000034971), OLFM2 (ENSG00000105088), OLFML3 (ENSG00000116774), OLFM3 (ENSG00000118733), OLFM1 (ENSG00000130558), OLFML2B (ENSG00000162745), OLFML1 (ENSG00000183801), OLFML2A (ENSG00000185585), GLDN (ENSG00000186417)

Protein

Protein identifiers

Olfactomedin-4 — Q6UX06 (reviewed: Q6UX06)

Alternative names: Antiapoptotic protein GW112, G-CSF-stimulated clone 1 protein, hOLfD

All UniProt accessions (1): Q6UX06

UniProt curated annotations — full annotation on UniProt →

Function. May promote proliferation of pancreatic cancer cells by favoring the transition from the S to G2/M phase. In myeloid leukemic cell lines, inhibits cell growth and induces cell differentiation and apoptosis. May play a role in the inhibition of EIF4EBP1 phosphorylation/deactivation. Facilitates cell adhesion, most probably through interaction with cell surface lectins and cadherin.

Subunit / interactions. Homomultimer; disulfide-linked. Interacts with NDUFA13. Interacts with cell surface lectins (locutions ricinus communis agglutinin I, concanavalin-A and wheat germ agglutinin) and cadherin.

Subcellular location. Secreted. Extracellular space. Mitochondrion.

Tissue specificity. Expressed during myeloid lineage development. Much higher expression in bone marrow neutrophils than in peripheral blood neutrophils (at protein level). Strongly expressed in the prostate, small intestine and colon and moderately expressed in the bone marrow and stomach. Overexpressed in some pancreatic cancer tissues.

Post-translational modifications. N-glycosylated.

Domain organisation. The olfactomedin-like domain is involved in the interaction with cadherin.

Induction. By retinoic acid. This induction requires functional NFKB pathway.

RefSeq proteins (1): NP_006409* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003112	Olfac-like_dom	Domain
IPR011041	Quinoprot_gluc/sorb_DH_b-prop	Homologous_superfamily
IPR050605	Olfactomedin-like_domain	Family

Pfam: PF02191

UniProt features (16 total): mutagenesis site 5, glycosylation site 3, sequence conflict 2, signal peptide 1, chain 1, domain 1, coiled-coil region 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UX06-F1	83.34	0.60

Functional residue map

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

Disulfide bonds (1): 246–437

Glycosylation sites (3): 72, 136, 253

Mutagenesis-validated functional residues (5):

Position	Phenotype
85	abolishes secretion. no effect on multimer formation.
226	no effect on secretion. affects multimer formation.
246	abolishes secretion. no effect on multimer formation.
437	abolishes secretion. no effect on multimer formation.
83	abolishes secretion. no effect on multimer formation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 130 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, CHEOK_RESPONSE_TO_HD_MTX_UP, HNF1_Q6, LHX3_01, GOBP_POSITIVE_REGULATION_OF_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, NKX61_01, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_REGULATION_OF_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, BROWNE_HCMV_INFECTION_14HR_DN, WTGAAAT_UNKNOWN, TGACATY_UNKNOWN

GO Biological Process (6): immune response (GO:0006955), cell adhesion (GO:0007155), signal transduction (GO:0007165), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), negative regulation of immune response (GO:0050777), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026)

GO Molecular Function (3): structural molecule activity (GO:0005198), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (13): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), specific granule lumen (GO:0035580), specific granule (GO:0042581), intercellular bridge (GO:0045171), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
cellular process	2
immune system process	1
response to stimulus	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
negative regulation of immune system process	1
immune response	1
negative regulation of response to stimulus	1
regulation of immune response	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
molecular_function	1
cell adhesion molecule binding	1
binding	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular_component	1
secretory granule lumen	1
specific granule	1
secretory granule	1
extracellular vesicle	1
intracellular organelle lumen	1
tertiary granule	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OLFM4	CDH17	Q12864	819
OLFM4	LGR5	O75473	802
OLFM4	ASCL2	Q99929	775
OLFM4	NDUFA13	Q9P0J0	753
OLFM4	CHGA	P10645	705
OLFM4	LRIG1	Q96JA1	676
OLFM4	LCN2	P30150	639
OLFM4	MMP8	P22894	633
OLFM4	BMI1	P35226	608
OLFM4	R4GMX3	R4GMX3	608
OLFM4	LTF	P02788	606
OLFM4	RSPO1	Q2MKA7	599
OLFM4	HOPX	Q9BPY8	597
OLFM4	SMOC2	Q9H3U7	592
OLFM4	ATOH1	Q92858	572
OLFM4	AXIN2	Q9Y2T1	572

IntAct

117 interactions, top by confidence:

A	B	Type	Score
LDLRAD1	OLFM4	psi-mi:“MI:0915”(physical association)	0.780
OLFM4	LDLRAD1	psi-mi:“MI:0915”(physical association)	0.780
OLFM4	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
KASH5	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	KASH5	psi-mi:“MI:0915”(physical association)	0.560
SYNE4	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	TMEM130	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	LEUTX	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	CLSTN3	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	KIR3DL3	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	CLEC17A	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	TFR2	psi-mi:“MI:0915”(physical association)	0.560
TNFSF11	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	QPCTL	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	TSPAN18	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	ITM2C	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
CLDN7	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
OLFM4	CLTRN	psi-mi:“MI:0915”(physical association)	0.560
BSCL2	OLFM4	psi-mi:“MI:0915”(physical association)	0.560
PVR	OLFM4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (105): CCDC155 (Two-hybrid), SYNE4 (Two-hybrid), LDLRAD1 (Two-hybrid), RBPMS (Affinity Capture-MS), TOR3A (Affinity Capture-MS), NID2 (Affinity Capture-MS), TRUB2 (Affinity Capture-MS), RDH13 (Affinity Capture-MS), ZNF281 (Affinity Capture-MS), GNL3L (Affinity Capture-MS), WDR59 (Affinity Capture-MS), P3H4 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), MTFR1L (Affinity Capture-MS), DDX11L8 (Affinity Capture-MS)

ESM2 similar proteins: A2BD09, A4IIT5, A6QLD2, O18738, O70624, O75339, O88998, O93279, P05067, P15943, P53601, P63056, P63057, Q06335, Q06481, Q07081, Q0P3W2, Q0V9V5, Q14118, Q14956, Q28685, Q29243, Q29RB4, Q3UZZ4, Q3V1G4, Q5IS80, Q60495, Q62165, Q62609, Q66K08, Q68BL7, Q68BL8, Q6AY06, Q6P7C7, Q6UX06, Q701R2, Q863A3, Q8AXP2, Q8BHP7, Q90372

Diamond homologs: A2BD09, A4IIT5, A6QLD2, B0BNI5, B5MFE9, O70624, O88917, O88923, O88998, O94910, O95490, O95897, O97817, O97827, O97831, P63056, P63057, Q0P3W2, Q0V9V5, Q0VCP3, Q25C36, Q2PT31, Q3UZZ4, Q3V1G4, Q568Y7, Q594P2, Q62609, Q66H86, Q68BL7, Q68BL8, Q6UWY5, Q6UX06, Q80TR1, Q80TS3, Q863A3, Q866N2, Q8BHP7, Q8BK62, Q8BM13, Q8JZZ7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
positive regulation of canonical NF-kappaB signal transduction	5	8.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1527771	GRCh37/hg19 13q14.11-31.3(chr13:42457841-91796698)	Pathogenic

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
13:53034346:A:AG	acceptor_gain	1.0000
13:53034346:AGTT:A	acceptor_gain	1.0000
13:53034347:G:GT	acceptor_gain	1.0000
13:53034347:GT:G	acceptor_gain	1.0000
13:53034347:GTT:G	acceptor_gain	1.0000
13:53034347:GTTG:G	acceptor_gain	1.0000
13:53034347:GTTGT:G	acceptor_gain	1.0000
13:53034499:AA:A	donor_gain	1.0000
13:53034499:AAG:A	donor_loss	1.0000
13:53034500:AGTAA:A	donor_loss	1.0000
13:53034501:G:GG	donor_gain	1.0000
13:53034501:GTAA:G	donor_loss	1.0000
13:53034502:T:A	donor_loss	1.0000
13:53042121:AGG:A	donor_loss	1.0000
13:53042124:T:G	donor_loss	1.0000
13:53043101:TTAG:T	acceptor_loss	1.0000
13:53043103:A:AG	acceptor_gain	1.0000
13:53043103:A:T	acceptor_loss	1.0000
13:53043104:G:GA	acceptor_gain	1.0000
13:53043104:GATA:G	acceptor_gain	1.0000
13:53043104:GATAA:G	acceptor_gain	1.0000
13:53043262:CAGGT:C	donor_loss	1.0000
13:53043263:AGGT:A	donor_loss	1.0000
13:53043265:G:GG	donor_gain	1.0000
13:53043266:T:A	donor_loss	1.0000
13:53028824:C:G	donor_gain	0.9900
13:53028837:A:G	donor_gain	0.9900
13:53034342:TTGCA:T	acceptor_loss	0.9900
13:53034343:TGCAG:T	acceptor_loss	0.9900
13:53034344:GCAGT:G	acceptor_loss	0.9900

AlphaMissense

3357 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:53034424:T:G	F94C	0.995
13:53041962:T:C	L137P	0.995
13:53050355:T:C	F373L	0.994
13:53050357:T:A	F373L	0.994
13:53050357:T:G	F373L	0.994
13:53042070:T:C	L173P	0.993
13:53043136:T:C	L201P	0.992
13:53050519:A:C	K427N	0.992
13:53050519:A:T	K427N	0.992
13:53050538:T:C	F434L	0.992
13:53050540:C:A	F434L	0.992
13:53050540:C:G	F434L	0.992
13:53034396:T:A	C85S	0.991
13:53034397:G:C	C85S	0.991
13:53050569:G:C	R444P	0.991
13:53043172:G:C	R213P	0.990
13:53034396:T:C	C85R	0.989
13:53034423:T:C	F94L	0.989
13:53034425:T:A	F94L	0.989
13:53034425:T:G	F94L	0.989
13:53050417:G:C	W393C	0.989
13:53050417:G:T	W393C	0.989
13:53050559:T:G	Y441D	0.989
13:53050598:T:C	F454L	0.989
13:53050600:T:A	F454L	0.989
13:53050600:T:G	F454L	0.989
13:53050027:C:A	N263K	0.988
13:53050027:C:G	N263K	0.988
13:53050415:T:A	W393R	0.988
13:53050415:T:C	W393R	0.988

dbSNP variants (sampled 300 via entrez): RS1000076130 (13:53032977 C>T), RS1000149568 (13:53033380 T>C), RS1000418724 (13:53027505 C>T), RS1000799525 (13:53034993 C>T), RS1000807068 (13:53030171 T>C), RS1000996147 (13:53039543 G>A), RS1001067383 (13:53045811 T>C), RS1001345152 (13:53039303 A>G), RS1001553455 (13:53045351 C>T), RS1001688266 (13:53051698 A>G), RS1001855453 (13:53033293 A>C), RS1001884000 (13:53046979 A>C), RS1002208752 (13:53033504 T>C,G), RS1002282479 (13:53033820 G>A), RS1002363887 (13:53028153 C>A,G,T)

Disease associations

OMIM: gene MIM:614061 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

42 associations (top):

Study	Trait	p-value
GCST001475_1	Obesity	2.000000e-09
GCST001547_4	Immune response to anthrax vaccine	8.000000e-06
GCST001762_925	Obesity-related traits	5.000000e-06
GCST001953_8	Obesity	2.000000e-09
GCST002337_100	Amyotrophic lateral sclerosis (sporadic)	1.000000e-07
GCST002461_18	Body mass index	4.000000e-06
GCST002783_17	Body mass index	9.000000e-08
GCST002783_363	Body mass index	3.000000e-13
GCST002783_498	Body mass index	1.000000e-12
GCST002783_93	Body mass index	2.000000e-08
GCST002894_4	Body mass index	1.000000e-08
GCST002894_5	Body mass index	6.000000e-09
GCST003177_8	Childhood body mass index	2.000000e-14
GCST004065_64	Waist circumference	2.000000e-09
GCST004065_69	Waist circumference	3.000000e-06
GCST004066_120	Hip circumference	5.000000e-10
GCST004066_45	Hip circumference	7.000000e-08
GCST004070_10	Cerebrospinal P-tau181p levels	6.000000e-09
GCST004495_68	BMI (adjusted for smoking behaviour)	4.000000e-09
GCST004495_69	BMI (adjusted for smoking behaviour)	2.000000e-06
GCST004497_24	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-08
GCST004497_25	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-06
GCST004499_93	BMI in non-smokers	6.000000e-08
GCST004557_104	Body mass index	4.000000e-06
GCST004557_205	Body mass index	3.000000e-06
GCST004557_22	Body mass index	5.000000e-08
GCST004557_234	Body mass index	4.000000e-08
GCST004558_101	Body mass index (joint analysis main effects and physical activity interaction)	8.000000e-06
GCST004558_154	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-07
GCST004558_19	Body mass index (joint analysis main effects and physical activity interaction)	5.000000e-07

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0005116	urinary metabolite measurement
EFO:0004340	body mass index
EFO:0004763	p-tau measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004337	intelligence
EFO:0008579	risk-taking behaviour
EFO:0009819	comparative body size at age 10, self-reported
EFO:0010100	multisite chronic pain

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	increases expression	2
Tretinoin	increases expression	2
Valproic Acid	affects expression, decreases methylation	2
tungsten carbide	affects binding, decreases expression	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
afimoxifene	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
5-iodotubercidin	decreases expression	1
ICI 164384	decreases reaction, increases expression, increases reaction	1
arsenic disulfide	affects expression	1
CGP 52608	affects binding, increases reaction	1
Zoledronic Acid	increases expression	1
Cadmium	increases expression, increases abundance	1
Cobalt	affects binding, decreases expression	1
Dexamethasone	increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Estradiol	increases reaction, decreases reaction, increases expression	1
Nicotine	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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