ENTREP3

Summary

ENTREP3 (endosomal transmembrane epsin interactor 3, HGNC:1233) is a protein-coding gene on chromosome 1q22, encoding Protein ENTREP3 (P81408).

This gene is located near the gene for the lysosomal enzyme glucosylceramidase; a deficiency in this enzyme is associated with Gaucher disease. The encoded protein has been identified as a potential binding partner of a WW domain-containing protein which is involved in apoptosis and tumor suppression. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10712 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 123 total
• GTEx eGene: eQTL in 22 tissues, sQTL in 8 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.90 (unconstrained)
• MANE Select transcript: NM_006589
• Notable: 123 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1233
Approved symbol	ENTREP3
Name	endosomal transmembrane epsin interactor 3
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	cote1
Ensembl gene	ENSG00000160767
Ensembl biotype	protein_coding
OMIM	619447
Entrez	10712

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 25 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000361361

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 2, TSL 5: 2

ENST00000361361, ENST00000350210, ENST00000368366, ENST00000368368, ENST00000472550, ENST00000481822, ENST00000487649, ENST00000491082, ENST00000497941, ENST00000706772, ENST00000706773, ENST00000706774, ENST00000851432, ENST00000851433, ENST00000851434, ENST00000851435, ENST00000851436, ENST00000851437, ENST00000851438, ENST00000851439, ENST00000851440, ENST00000851441, ENST00000927590, ENST00000927591, ENST00000927592, ENST00000927593, ENST00000927594, ENST00000927595, ENST00000927596, ENST00000927597, ENST00000927598, ENST00000965815, ENST00000974295, ENST00001025893, ENST00001070878, ENST00001070879, ENST00001070880, ENST00001145293

RefSeq mRNA: 3 — MANE Select: NM_006589 NM_001267608, NM_006589, NM_198264

CCDS: CCDS1103, CCDS1104, CCDS58035

Canonical transcript exons

ENST00000361361 — 12 exons

Exon	Start	End
ENSE00001225815	155250276	155250821
ENSE00001841249	155247205	155247955
ENSE00003462917	155251095	155251164
ENSE00003532182	155248050	155248303
ENSE00003538787	155251502	155251601
ENSE00003555746	155251733	155251905
ENSE00003598379	155253625	155253732
ENSE00003614003	155248405	155248473
ENSE00003643914	155254400	155254456
ENSE00003680590	155253859	155253978
ENSE00003684016	155254084	155254194
ENSE00003751957	155254653	155255483

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 91.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.6119 / max 189.9289, expressed in 1810 samples.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, cerebellum, lower esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ENTREP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 22 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	eqtl	2.9e-12	+0.21	1:155252386:C:T
Artery Tibial	eqtl	7.5e-11	+0.15	1:155248655:A:G
Nerve Tibial	eqtl	1.3e-07	+0.16	1:155248655:A:G
Adipose Subcutaneous	eqtl	3.8e-07	+0.14	1:155283042:G:A
Esophagus Muscularis	eqtl	7.8e-07	+0.17	1:155254510:C:A
Brain Cortex	eqtl	1.1e-06	+0.20	1:155247644:AGG:A
Testis	eqtl	9.1e-05	-0.65	1:155752903:G:A
Brain Frontal Cortex BA9	eqtl	1.7e-04	+0.90	1:154954410:T:C
Colon Sigmoid	eqtl	1.7e-04	+0.13	1:155229524:C:G
Esophagus Gastroesophageal Junction	eqtl	3.2e-04	+0.17	1:155247644:AGG:A
Artery Tibial	sqtl	1.0e-03	+0.29	1:155248377:T:C
Esophagus Muscularis	sqtl	1.0e-03	+0.36	1:155604680:C:A
Brain Cerebellar Hemisphere	sqtl	1.3e-03	+0.37	1:155260340:C:T
Colon Transverse	sqtl	7.8e-03	+0.50	1:154419406:G:A
Spleen	eqtl	7.9e-03	-0.16	1:155252939:G:A
Cells Cultured fibroblasts	sqtl	9.9e-03	+0.28	1:155248377:T:C
Artery Aorta	sqtl	1.2e-02	+0.35	1:155280900:A:T
Adipose Visceral Omentum	eqtl	1.3e-02	+0.37	1:155299989:G:A
Colon Transverse	eqtl	1.3e-02	+0.09	1:155305169:G:C
Lung	eqtl	1.5e-02	-0.37	1:156038197:G:A

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
14942	33.4917	1810
14941	0.2831	121
14937	0.2553	122
14940	0.2060	71
14939	0.1598	61
201749	0.1271	35
14938	0.0568	11
14943	0.0322	6

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	91.38	gold quality
cerebellar hemisphere	UBERON:0002245	90.99	gold quality
cerebellar cortex	UBERON:0002129	90.94	gold quality
cerebellum	UBERON:0002037	90.93	gold quality
lower esophagus mucosa	UBERON:0035834	90.58	gold quality
right frontal lobe	UBERON:0002810	89.60	gold quality
apex of heart	UBERON:0002098	89.07	gold quality
gastrocnemius	UBERON:0001388	89.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.82	gold quality
lower esophagus	UBERON:0013473	88.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.70	gold quality
stromal cell of endometrium	CL:0002255	88.43	gold quality
frontal cortex	UBERON:0001870	88.34	gold quality
anterior cingulate cortex	UBERON:0009835	88.11	gold quality
right adrenal gland cortex	UBERON:0035827	88.09	gold quality
primary visual cortex	UBERON:0002436	88.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.92	gold quality
right adrenal gland	UBERON:0001233	87.86	gold quality
prefrontal cortex	UBERON:0000451	87.76	gold quality
cerebral cortex	UBERON:0000956	87.75	gold quality
right coronary artery	UBERON:0001625	87.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.62	gold quality
muscle of leg	UBERON:0001383	87.59	gold quality
superior frontal gyrus	UBERON:0002661	87.54	gold quality
mucosa of stomach	UBERON:0001199	87.42	gold quality
fundus of stomach	UBERON:0001160	87.36	gold quality
brain	UBERON:0000955	87.15	gold quality
popliteal artery	UBERON:0002250	87.13	gold quality
tibial artery	UBERON:0007610	87.12	gold quality
esophagus	UBERON:0001043	87.11	gold quality
left coronary artery	UBERON:0001626	86.99	gold quality
temporal lobe	UBERON:0001871	86.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.93	gold quality
amygdala	UBERON:0001876	86.88	gold quality
Ammon’s horn	UBERON:0001954	86.75	gold quality
myometrium	UBERON:0001296	86.67	gold quality
thoracic aorta	UBERON:0001515	86.67	gold quality
descending thoracic aorta	UBERON:0002345	86.61	gold quality
ascending aorta	UBERON:0001496	86.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.32	gold quality
putamen	UBERON:0001874	86.30	gold quality
mucosa of transverse colon	UBERON:0004991	86.23	gold quality
hypothalamus	UBERON:0001898	86.16	gold quality
nucleus accumbens	UBERON:0001882	86.14	gold quality
esophagus mucosa	UBERON:0002469	86.09	gold quality
left adrenal gland	UBERON:0001234	86.04	gold quality
left adrenal gland cortex	UBERON:0035825	86.04	gold quality
caudate nucleus	UBERON:0001873	86.01	gold quality
body of uterus	UBERON:0009853	85.95	gold quality
skeletal muscle tissue	UBERON:0001134	85.89	gold quality
metanephros cortex	UBERON:0010533	85.89	gold quality
body of stomach	UBERON:0001161	85.87	gold quality
pituitary gland	UBERON:0000007	85.84	gold quality
adenohypophysis	UBERON:0002196	85.55	gold quality
ventricular zone	UBERON:0003053	85.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.93	gold quality
cortical plate	UBERON:0005343	84.76	gold quality
endocervix	UBERON:0000458	84.65	gold quality
colon	UBERON:0001155	84.53	gold quality
ectocervix	UBERON:0012249	84.53	gold quality
prostate gland	UBERON:0002367	84.50	gold quality
urinary bladder	UBERON:0001255	84.49	gold quality
muscle tissue	UBERON:0002385	84.34	gold quality
adrenal gland	UBERON:0002369	84.29	gold quality
vagina	UBERON:0000996	84.27	gold quality
substantia nigra	UBERON:0002038	84.25	gold quality
cortex of kidney	UBERON:0001225	84.19	gold quality
right ovary	UBERON:0002118	84.14	gold quality
heart left ventricle	UBERON:0002084	84.01	gold quality
multicellular organism	UBERON:0000468	83.75	gold quality
stomach	UBERON:0000945	83.74	gold quality
uterine cervix	UBERON:0000002	83.46	gold quality
tibial nerve	UBERON:0001323	83.45	gold quality
transverse colon	UBERON:0001157	83.44	gold quality
omental fat pad	UBERON:0010414	83.44	gold quality
ganglionic eminence	UBERON:0004023	83.42	gold quality
left ovary	UBERON:0002119	83.16	gold quality
left uterine tube	UBERON:0001303	83.10	gold quality
adipose tissue	UBERON:0001013	83.06	gold quality
skin of leg	UBERON:0001511	83.00	gold quality
intestine	UBERON:0000160	82.99	gold quality
heart	UBERON:0000948	82.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.81	gold quality
right atrium auricular region	UBERON:0006631	82.73	gold quality
zone of skin	UBERON:0000014	82.71	gold quality
granulocyte	CL:0000094	82.68	gold quality
skin of abdomen	UBERON:0001416	82.67	gold quality
adult mammalian kidney	UBERON:0000082	82.66	gold quality
ovary	UBERON:0000992	82.58	gold quality
upper lobe of left lung	UBERON:0008952	81.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.83	gold quality
right lobe of thyroid gland	UBERON:0001119	81.77	gold quality
minor salivary gland	UBERON:0001830	81.74	gold quality
saliva-secreting gland	UBERON:0001044	81.51	gold quality
small intestine	UBERON:0002108	81.51	gold quality
right testis	UBERON:0004534	81.11	gold quality
right uterine tube	UBERON:0001302	81.05	gold quality
thoracic mammary gland	UBERON:0005200	80.98	gold quality
left lobe of thyroid gland	UBERON:0001120	80.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.70

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Postcentral gyrus	tissue	33.3
Spinal cord	tissue	28.4
Locus coeruleus	tissue	24.3
Hippocampus	tissue	22.4
Frontal cortex	tissue	20.9
Caudate putamen	tissue	20.5
Skeletal muscle	tissue	17.0
Nucleus accumbens	tissue	16.2
Pituitary gland	tissue	12.8
Medulla oblongata	tissue	12.8
Vagina	tissue	12.4
Corpus callosum	tissue	11.4
Superior colliculi	tissue	10.7
Substantia nigra	tissue	10.6
Midbrain	tissue	10.3
Pons	tissue	10.1
Cerebral cortex	tissue	9.7
Somatosensory cortex	tissue	9.7
Thalamus	tissue	9.6
Hippocampal formation	tissue	8.9
Insular cortex	tissue	8.8
Temporal cortex	tissue	8.7
Choroid plexus	tissue	8.6
Occipital cortex	tissue	8.6
Amygdala	tissue	8.4
Motor cortex	tissue	8.2
Putamen	tissue	8.2
Entorhinal cortex	tissue	8.2
Prefrontal cortex	tissue	8.0
Retrosplenial cortex	tissue	7.9
Retrosplenial and cingulate cortex	tissue	7.8
Periaqueductal gray	tissue	7.4
Hypothalamus	tissue	7.3
Ventral forebrain	tissue	7.0
Adipose tissue	tissue	6.8
Parathyroid gland	tissue	6.6
Basal ganglia	tissue	6.5
Duodenum	tissue	6.4
Tongue	tissue	6.2
Septum	tissue	6.2
Cerebellum	tissue	5.9
Adrenal gland	tissue	5.9
Smooth muscle	tissue	5.8
Stomach 1	tissue	5.5
Seminal vesicle	tissue	5.5
Small intestine	tissue	5.5
Appendix	tissue	5.0
Testis	tissue	4.9
Ovary	tissue	4.9
Olfactory bulb	tissue	4.9
Placenta	tissue	4.7
Endometrium 1	tissue	4.6
Kidney	tissue	4.6
Prostate	tissue	4.4
Skin 1	tissue	4.3
Pancreas	tissue	4.3
Salivary gland	tissue	4.1
Urinary bladder	tissue	3.9
Spleen	tissue	3.9
Cervix	tissue	3.8

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Lateral vestibular nucleus (43.2), Ventral posterolateral thalamic nucleus (40.9), Precentral gyrus (40.2), Spinal trigeminal nucleus, interpolar (35.8), Lateral geniculate body (35.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ENTREP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 54 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-543	99.52	69.03	2595

Functional genomics

gnomAD constraint: pLI 3.01e-09, LOEUF 0.897, missense Z -0.3 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000361361 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 5)

• Overexpression of COTE1 promotes cellular invasion of hepatocellular carcinoma. (PMID:23317259)
• our findings suggest that the cytoplasmic protein COTE1 contributes to hepatocellular carcinoma tumorigenesis by regulating cell proliferation through the modulation of WWOX signaling (PMID:24899407)
• High FAM189B Expression and Its Prognostic Value in Patients with Gastric Cancer. (PMID:34124264)
• COTE-1 promotes the proliferation and invasion of small cell lung cancer by regulating autophagy activity via the AMPK/mTOR signaling pathway. (PMID:37454876)
• COTE1 Facilitates Intrahepatic Cholangiocarcinoma Progression via Beclin1-Dependent Autophagy Inhibition. (PMID:37780485)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam189b	ENSDARG00000079008
mus_musculus	Entrep3	ENSMUSG00000032657
rattus_norvegicus	Entrep3	ENSRNOG00000020518

Paralogs (2): ENTREP2 (ENSG00000104059), ENTREP1 (ENSG00000135063)

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CLK2	protein-coding	1196
GBA1	protein-coding	2629
PKLR	protein-coding	5313
HCN3	protein-coding	57657
SCAMP3	protein-coding	10067
THBS3-AS1	ncRNA	105371450
MTX1	protein-coding	4580
THBS3	protein-coding	7059
FDPS	protein-coding	2224
RUSC1-AS1	ncRNA	284618

Protein

Protein identifiers

Protein ENTREP3 — P81408 (reviewed: P81408)

Alternative names: Endosomal transmembrane epsin interactor 3, Protein COTE1

All UniProt accessions (3): P81408, D6RD59, Q96AD8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. May interact with WWOX.

Subcellular location. Membrane.

Tissue specificity. Widely expressed.

Similarity. Belongs to the ENTREP family.

Isoforms (4)

UniProt ID	Names	Canonical?
P81408-1	A	yes
P81408-2	B
P81408-3	2
P81408-4	3

RefSeq proteins (3): NP_001254537, NP_006580, NP_937995 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007237	CD20-like_TM	Domain
IPR030431	ENTREP1-3	Family

Pfam: PF04103

UniProt features (23 total): region of interest 5, transmembrane region 4, modified residue 4, splice variant 3, sequence variant 3, compositionally biased region 2, chain 1, glycosylation site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P81408-F1	53.93	0.10

Human Protein Atlas

Protein class: Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH uncertain · IF supported

Functional residue map

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

Post-translational modifications (4)

Type	Positions
Phosphoserine	358, 389, 493, 574

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	160

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 162 (showing top): MORF_RAGE, GCANCTGNY_MYOD_Q6, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, PATIL_LIVER_CANCER, MORF_FANCG, chr1q22, DASU_IL6_SIGNALING_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MORF_PML, MORF_IKBKG, MORF_MT4, MORF_ORC1L, TCCCRNNRTGC_UNKNOWN, MARSON_BOUND_BY_E2F4_UNSTIMULATED

GO Molecular Function (2): WW domain binding (GO:0050699), protein binding (GO:0005515)

GO Cellular Component (2): nucleoplasm (GO:0005654), membrane (GO:0016020)

GO top-level categories

4 GO namespaces:

Category	Terms
cellular anatomical structure	2
protein domain specific binding	1
binding	1
nuclear lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 4 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
nucleoplasm	CC	direct assay
WW domain binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 422 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENTREP3	SCAMP3	O14828	531
ENTREP3	KRTCAP2	Q8N6L1	495
ENTREP3	A0A2R8YDH4	A0A2R8YDH4	494
ENTREP3	N4BP1	O75113	454
ENTREP3	NDFIP2	Q9NV92	446
ENTREP3	SYNRG	Q9UMZ2	439
ENTREP3	JAGN1	Q8N5M9	407
ENTREP3	THBS3	P49746	400
ENTREP3	NUP210L	Q5VU65	398
ENTREP3	DPM3	Q9P2X0	393
ENTREP3	MTX1	Q13505	389
ENTREP3	LETMD1	Q6P1Q0	375
ENTREP3	HCN3	Q9P1Z3	361
ENTREP3	CPHXL	A0A1W2PPM1	346
ENTREP3	GBA1	P04062	338

IntAct

Human interaction partners of ENTREP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
WWOX	association	0.720	3
NEDD4	association	0.530	3
YAP1	direct interaction	0.440	1
SCRIB	physical association	0.400	1
WWP2	association	0.350	1

Disease & clinical

Genetic variants

Variant evidence for ENTREP3: 123 ClinVar records (0 pathogenic / likely pathogenic); 17 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 879):

Position(s)	Effect	Δscore	Sites
1:155248048–155248049	donor_loss	1.0000	4
1:155248304–155248305	acceptor_loss	1.0000	3
1:155248404	donor_loss	1.0000
1:155248474–155248475	acceptor_loss	1.0000	6
1:155250623	donor_gain	1.0000
1:155251093–155251094	donor_loss	1.0000	4
1:155251165–155251166	acceptor_loss	1.0000	6
1:155251500–155251501	donor_loss	1.0000	5
1:155251602–155251603	acceptor_loss	1.0000	3
1:155251609	acceptor_gain	1.0000

AlphaMissense

1,164 missense substitutions predicted likely pathogenic (of 4,223 scored), across 301 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D262	8	0.956	0.992
F241	8	0.929	0.996
D360	8	0.922	0.985
F98	8	0.878	0.977
S52	8	0.866	0.999
D346	8	0.857	0.966
S370	8	0.842	0.987
C138	7	0.977	0.991
C129	7	0.974	0.989
C136	7	0.970	0.989
C163	7	0.970	0.983
F364	7	0.968	0.987
C404	7	0.968	0.987
C257	7	0.965	0.991
W71	7	0.959	0.997
C422	7	0.958	0.980
E254	7	0.946	0.979
S258	7	0.935	0.998
C375	7	0.927	0.978
W87	7	0.914	0.981

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000728
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000949

Disease associations

OMIM: gene MIM:619447 | disease phenotypes:

GWAS associations

17 associations:

Study	Trait	p-value
GCST007294_150	Body fat distribution (trunk fat ratio)	8e-35
GCST007295_72	Body fat distribution (leg fat ratio)	1e-28
GCST007294_159	Body fat distribution (trunk fat ratio)	6e-21
GCST007295_112	Body fat distribution (leg fat ratio)	7e-17
GCST010700_5	Cortical thickness (MOSTest)	8e-17
GCST007294_25	Body fat distribution (trunk fat ratio)	1e-15
GCST007324_54	Adventurousness	2e-15
GCST010703_205	Brain morphology (MOSTest)	4e-14
GCST007295_17	Body fat distribution (leg fat ratio)	3e-13
GCST010696_10	Cortical thickness (min-P)	2e-10
GCST010697_21	Cortical surface area (min-P)	3e-10
GCST010702_25	Subcortical volume (MOSTest)	3e-10
GCST010699_50	Brain morphology (min-P)	7e-10
GCST010698_84	Subcortical volume (min-P)	9e-10
GCST010701_97	Cortical surface area (MOSTest)	1e-9
GCST004131_70	Inflammatory bowel disease	6e-8
GCST004132_19	Crohn’s disease	2e-7

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0008579	risk-taking behaviour
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	2
Cadmium Chloride	decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Diazinon	increases methylation	1
Fonofos	increases methylation	1
Endosulfan	increases expression	1
Fluorouracil	affects response to substance	1
Lead	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.