GRB14

Summary

GRB14 (growth factor receptor bound protein 14, HGNC:4565) is a protein-coding gene on chromosome 2q24.3, encoding Growth factor receptor-bound protein 14 (Q14449). Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways.

The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor signaling. This gene may play a role in signaling pathways that regulate growth and metabolism. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2888 — RefSeq curated summary.

At a glance

• GWAS associations: 175
• Clinical variants (ClinVar): 111 total — 1 pathogenic
• MANE Select transcript: NM_004490

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4565
Approved symbol	GRB14
Name	growth factor receptor bound protein 14
Location	2q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115290
Ensembl biotype	protein_coding
OMIM	601524
Entrez	2888

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000263915, ENST00000424693, ENST00000446413, ENST00000469573, ENST00000488342, ENST00000497306, ENST00000696453, ENST00000894024, ENST00000894025, ENST00000894026, ENST00000894027, ENST00000911821, ENST00000911822, ENST00000943511, ENST00000943512, ENST00000943513, ENST00000943514

RefSeq mRNA: 2 — MANE Select: NM_004490 NM_001303422, NM_004490

CCDS: CCDS2222, CCDS92883

Canonical transcript exons

ENST00000263915 — 14 exons

Exon	Start	End
ENSE00000779604	164508455	164508550
ENSE00001193732	164621119	164621482
ENSE00003459758	164497374	164497490
ENSE00003504471	164527014	164527135
ENSE00003533149	164525004	164525078
ENSE00003537972	164619687	164619819
ENSE00003549431	164508742	164508852
ENSE00003579337	164497211	164497283
ENSE00003593331	164521980	164522117
ENSE00003626853	164494431	164494524
ENSE00003640461	164547660	164547816
ENSE00003681686	164502255	164502335
ENSE00003786048	164497008	164497095
ENSE00003967433	164492417	164493182

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 97.26.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5211 / max 120.8659, expressed in 801 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31613	1.4722	678
31612	0.3948	201
31608	0.3760	73
31611	0.1236	52
31607	0.0697	12
31609	0.0544	23
31610	0.0304	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.26	gold quality
right lobe of liver	UBERON:0001114	97.25	gold quality
metanephros cortex	UBERON:0010533	95.06	gold quality
corpus epididymis	UBERON:0004359	94.26	gold quality
left adrenal gland cortex	UBERON:0035825	93.44	gold quality
left adrenal gland	UBERON:0001234	93.26	gold quality
right adrenal gland	UBERON:0001233	93.18	gold quality
liver	UBERON:0002107	93.05	gold quality
adrenal cortex	UBERON:0001235	93.03	gold quality
right adrenal gland cortex	UBERON:0035827	92.64	gold quality
right testis	UBERON:0004534	92.45	gold quality
body of tongue	UBERON:0011876	92.37	gold quality
renal medulla	UBERON:0000362	92.31	gold quality
left testis	UBERON:0004533	92.23	gold quality
body of pancreas	UBERON:0001150	92.13	gold quality
adrenal gland	UBERON:0002369	91.80	gold quality
adult mammalian kidney	UBERON:0000082	91.33	gold quality
testis	UBERON:0000473	90.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.90	gold quality
kidney	UBERON:0002113	89.39	gold quality
nephron tubule	UBERON:0001231	87.55	gold quality
cortex of kidney	UBERON:0001225	87.34	gold quality
apex of heart	UBERON:0002098	87.10	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.70	gold quality
metanephros	UBERON:0000081	86.69	gold quality
diaphragm	UBERON:0001103	86.66	gold quality
pancreas	UBERON:0001264	86.32	gold quality
heart left ventricle	UBERON:0002084	85.57	gold quality
cardiac ventricle	UBERON:0002082	85.29	gold quality
endometrium epithelium	UBERON:0004811	85.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	56.37
E-ANND-3	yes	6.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, FOXO3

miRNA regulators (miRDB)

15 targeting GRB14, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-5583-5P	97.85	67.61	1243
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-1249-3P	90.34	67.26	42
HSA-MIR-6726-3P	83.39	62.13	46

Literature-anchored findings (GeneRIF, showing 21)

• serves as an adaptor protein to recruit 3-phosphoinositede-dependent kinase-1 to activated insulin receptor, thus promoting Akt phosphorylation and transduction of the insulin signal (PMID:15210700)
• regulation of Grb14 expression levels in response to hormonal stimuli, and are consistent with its role as a repressor of insulin signaling where it is induced as a negative feedback mechanism. (PMID:15372466)
• Grb14 may regulate signalling through the insulin receptor by controlling its tyrosine dephosphorylation in a site-specific manner. (PMID:16582879)
• GRB14 is a weight-loss-responsive gene in skeletal muscle. Its observed transcriptional modulation may improve insulin signaling, with weight loss. (PMID:16849634)
• Grb14 regulates insulin action at two levels, through insulin receptors binding and by interfering with downstream pathways. (PMID:19359342)
• Results illuminate the membrane-recruitment mechanisms of Grb7, Grb10 and Grb14. (PMID:19648926)
• Grb14 was recruited to FGFR1 into a trimeric complex containing also phospholipase C gamma (PMID:20932831)
• A new role for Grb14 in finely tuning receptor signaling and modulating thyroid cancer progression. (PMID:22158039)
• Grb14 is the first negative regulator of CEACAM3-initiated bacterial phagocytosis and might help to focus granulocyte responses to the subcellular sites of pathogen-host cell contact (PMID:22948154)
• Studies indicate that insulin receptor (IR) and IGF Type 1 Receptor (IGFR) have been identified as important partners of Grb10/14 and SH2B1/B2 adaptors. (PMID:23190452)
• ANKRD55 rs459193 and GRB14 rs13389219 associate with insulin resistance. (PMID:23457408)
• Genes within recently identified loci associated with waist-hip ratio (WHR) exhibit fat depot-specific mRNA expression, which correlates with obesity-related traits. Adipose tissue (AT) mRNA expression of 6 genes (TBX15/WARS2, STAB1, PIGC, ZNRF3, GRB14 (PMID:23670221)
• Modulation of mouse rod photoreceptor responses by Grb14 protein. (PMID:24273167)
• Phosphorylation of Grb14 BPS domain by GSK-3 correlates with complex forming of Grb14 and insulin receptor. (PMID:24535599)
• Colorectal cancer patients with high GRB14 levels had a shorter survival and GRB14 was upregulated at an advanced clinical stage with enhanced tumor invasion and lymph node metastasis. (PMID:26965150)
• We investigated the modification of air pollution and diabetes association by a genetic risk score covering 63 T2D genes. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A and KCNQ1 showed nominally significant interactions with PM10 (P<0.05). Our results suggest that genetic risk for T2D may modify susceptibility to air pollution through alterations in insulin sensitivity. (PMID:27281273)
• The N-terminus of the BPS domain plays an important role in the regulation of human Grb14 and insulin receptor complex formation through phosphorylation, in addition to other domains. (PMID:28130417)
• Data suggest that GRB10 and GRB14 are both Ca2+-dependent CaM-binding proteins; more than one CaM-binding site and/or accessory CaM-binding sites appear to exist in GRB10 and GRB14, as compared to a single one present in GRB7. (GRB10 = growth factor receptor-bound protein 10; GRB14 = growth factor receptor-bound protein 14; CaM = calmodulin; GRB7 = growth factor receptor-bound protein 7) (PMID:28295264)
• These findings suggested that phosphate groups on Ser(358) and Ser(362) in hGrb14 are dephosphorylated by PP1, and the dephosphorylation facilitates hGrb14-IR complex formation. (PMID:31347216)
• Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRalpha pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance. (PMID:33867829)
• Metabolic Effects of the Waist-To-Hip Ratio Associated Locus GRB14/COBLL1 Are Related to GRB14 Expression in Adipose Tissue. (PMID:35955692)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	GRB14	ENSDARG00000068280
mus_musculus	Grb14	ENSMUSG00000026888
rattus_norvegicus	Grb14	ENSRNOG00000052498
drosophila_melanogaster	pico	FBGN0261811
caenorhabditis_elegans		WBGENE00003243

Paralogs (4): APBB1IP (ENSG00000077420), GRB10 (ENSG00000106070), GRB7 (ENSG00000141738), RAPH1 (ENSG00000173166)

Protein

Protein identifiers

Growth factor receptor-bound protein 14 — Q14449 (reviewed: Q14449)

Alternative names: GRB14 adapter protein

All UniProt accessions (3): C9JD37, C9JLT6, Q14449

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal.

Subunit / interactions. Interacts with the cytoplasmic domain of the autophosphorylated insulin receptor (INSR), through the SH2 domain. Interacts with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop on INSR from dephosphorylation. Binds to the ankyrin repeat region of TNKS2 via its N-terminus. Interacts with activated NRAS. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated).

Subcellular location. Cytoplasm. Endosome membrane.

Tissue specificity. Expressed at high levels in the liver, kidney, pancreas, testis, ovary, heart and skeletal muscle.

Post-translational modifications. Phosphorylated on serine residues. Phosphorylated on tyrosine residues by TEK/TIE2.

Domain organisation. The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3.

Similarity. Belongs to the GRB7/10/14 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14449-1	1	yes
Q14449-2	2

RefSeq proteins (2): NP_001290351, NP_004481* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000980	SH2	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015042	BPS-dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035034	Grb14_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR039664	GRB/APBB1IP	Family
IPR039665	PH_APBB1IP	Domain

Pfam: PF00017, PF00169, PF08947, PF21989

UniProt features (59 total): strand 23, helix 10, mutagenesis site 7, turn 6, modified residue 4, domain 3, sequence variant 2, splice variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2AUG	X-RAY DIFFRACTION	2.3
4K81	X-RAY DIFFRACTION	2.4
2AUH	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14449-F1	78.37	0.56

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): 2, 9, 372, 375

Mutagenesis-validated functional residues (7):

Position	Phenotype
140	partial loss of insr-binding. loss of inhibition of akt1 activation. loss of inhibition of mapk3 phosphorylation. loss o
245	4-fold increase in pi(3,4,5)p3-binding affinity; when associated with s-246.
246	4-fold increase in pi(3,4,5)p3-binding affinity; when associated with g-245.
252	partial loss of insr-binding. loss of inhibition of akt1 activation. loss of inhibition of mapk3 phosphorylation. loss o
299	no effect on pi(3,4,5)p3-binding.
348	loss of inhibition of akt1 activation; when associated with a-349. loss of inhibition of mapk3 phosphorylation; when ass
349	loss of inhibition of akt1 activation; when associated with a-348. loss of inhibition of mapk3 phosphorylation; when ass

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-210993	Tie2 Signaling

MSigDB gene sets: 144 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GRUETZMANN_PANCREATIC_CANCER_DN, MODULE_64, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, REACTOME_TIE2_SIGNALING, MODULE_289, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_INSULIN, KOYAMA_SEMA3B_TARGETS_UP, chr2q24

GO Biological Process (3): signal transduction (GO:0007165), insulin receptor signaling pathway (GO:0008286), negative regulation of insulin receptor signaling pathway (GO:0046627)

GO Molecular Function (4): protein-macromolecule adaptor activity (GO:0030674), receptor tyrosine kinase binding (GO:0030971), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
protein binding	1
molecular adaptor activity	1
signaling receptor binding	1
protein tyrosine kinase binding	1
molecular_function	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1527 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRB14	FGFR1	P11362	886
GRB14	INSR	P06213	826
GRB14	TNKS2	Q9H2K2	802
GRB14	TNKS	O95271	740
GRB14	COBLL1	Q53SF7	700
GRB14	EGFR	P00533	651
GRB14	CNGA1	P29973	647
GRB14	LYPLAL1	Q5VWZ2	643
GRB14	PGK1	P00558	606
GRB14	HMG20A	Q9NP66	590
GRB14	SHC1	P29353	588
GRB14	ANKRD55	Q3KP44	584
GRB14	AP3S2	P59780	571
GRB14	IGF1	P01343	543
GRB14	ARL15	Q9NXU5	542

IntAct

25 interactions, top by confidence:

A	B	Type	Score
CSNK2A1	CSNK2B	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
GOLGA2	GRB14	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	GRB14	psi-mi:“MI:0915”(physical association)	0.560
STK26	GRB14	psi-mi:“MI:0915”(physical association)	0.490
GRB14	IGF1R	psi-mi:“MI:0915”(physical association)	0.490
GRB14	MET	psi-mi:“MI:0407”(direct interaction)	0.440
	GRB14	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GRB14	INSR	psi-mi:“MI:0915”(physical association)	0.400
NRAS	GRB14	psi-mi:“MI:0915”(physical association)	0.400
GRB14	FRS3	psi-mi:“MI:0915”(physical association)	0.370
GRB14	HCK	psi-mi:“MI:0915”(physical association)	0.370
CDC5L	GRB14	psi-mi:“MI:0915”(physical association)	0.370
GRB14	ALK	psi-mi:“MI:0915”(physical association)	0.370
GRB14	CFB	psi-mi:“MI:0914”(association)	0.350
INSR	GRB14	psi-mi:“MI:2364”(proximity)	0.270
GRB14	GSK3B	psi-mi:“MI:2364”(proximity)	0.270
GRB14	GOLGA2	psi-mi:“MI:0915”(physical association)	0.000
GRB14	TRIM27	psi-mi:“MI:0915”(physical association)	0.000
GRB14	NFKB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): CHFR (Affinity Capture-Western), CHFR (Reconstituted Complex), chfr (Reconstituted Complex), Chfr (Two-hybrid), STK26 (Two-hybrid), GRB14 (Two-hybrid), GRB14 (Two-hybrid), GRB14 (FRET), FGFR1 (Affinity Capture-Western), GRB14 (Affinity Capture-Western), GRB14 (Two-hybrid), GRB14 (Two-hybrid), GRB14 (FRET), GRB14 (Affinity Capture-Western), INSR (Affinity Capture-Western)

ESM2 similar proteins: A0A140LI67, B5KFD7, D4A7V9, M0R4F8, O08774, O35827, O43187, O70167, O70173, O88866, O88900, O95398, O95704, P0C5Y8, Q0P5I2, Q13322, Q14449, Q4QQS0, Q5BIW4, Q5ICW4, Q5JV73, Q5PQS0, Q5R810, Q60760, Q68DX3, Q6IFT4, Q6IRN0, Q6P4K6, Q6REY9, Q6S5L8, Q6TXD4, Q7TSI1, Q80TQ5, Q80VA5, Q8BW88, Q8CFA1, Q8IWE5, Q8R1C9, Q8R2S1, Q8VCC8

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
TEK	“up-regulates activity”	GRB14	phosphorylation
GSK3B	“down-regulates activity”	GRB14	phosphorylation
GSK3A	“down-regulates activity”	GRB14	phosphorylation
GRB14	“down-regulates activity”	INSR	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 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
protein autophosphorylation	6	54.5×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	90
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1526929	GRCh37/hg19 2q24.3(chr2:165428510-166888012)	Pathogenic

SpliceAI

3441 predictions. Top by Δscore:

Variant	Effect	Δscore
2:164493179:CTAC:C	acceptor_gain	1.0000
2:164493180:TAC:T	acceptor_gain	1.0000
2:164493180:TACCT:T	acceptor_loss	1.0000
2:164493181:AC:A	acceptor_gain	1.0000
2:164493182:CC:C	acceptor_gain	1.0000
2:164493182:CCTGC:C	acceptor_loss	1.0000
2:164493183:C:CC	acceptor_gain	1.0000
2:164494429:A:AC	donor_gain	1.0000
2:164494430:C:CC	donor_gain	1.0000
2:164494523:CT:C	acceptor_gain	1.0000
2:164494525:C:CC	acceptor_gain	1.0000
2:164497006:AC:A	donor_gain	1.0000
2:164497007:CC:C	donor_gain	1.0000
2:164497376:T:A	donor_gain	1.0000
2:164500231:T:TA	donor_gain	1.0000
2:164525074:AAATA:A	acceptor_gain	1.0000
2:164525075:AATA:A	acceptor_gain	1.0000
2:164525076:ATA:A	acceptor_gain	1.0000
2:164525077:TA:T	acceptor_gain	1.0000
2:164525079:C:CC	acceptor_gain	1.0000
2:164527009:CTTA:C	donor_loss	1.0000
2:164527010:TTA:T	donor_loss	1.0000
2:164527011:TA:T	donor_loss	1.0000
2:164527133:TTT:T	acceptor_gain	1.0000
2:164527133:TTTC:T	acceptor_loss	1.0000
2:164527134:TTCTG:T	acceptor_loss	1.0000
2:164527136:C:CC	acceptor_gain	1.0000
2:164527136:C:CG	acceptor_loss	1.0000
2:164527137:T:A	acceptor_loss	1.0000
2:164547654:CCTTA:C	donor_loss	1.0000

AlphaMissense

3573 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:164493067:A:G	L531S	1.000
2:164493102:G:C	F519L	1.000
2:164493102:G:T	F519L	1.000
2:164493104:A:G	F519L	1.000
2:164493112:A:G	L516P	1.000
2:164493129:A:C	F510L	1.000
2:164493129:A:T	F510L	1.000
2:164493130:A:G	F510S	1.000
2:164493131:A:G	F510L	1.000
2:164494477:A:G	L477P	1.000
2:164497075:A:G	W439R	1.000
2:164497075:A:T	W439R	1.000
2:164493103:A:G	F519S	0.999
2:164494477:A:T	L477Q	0.999
2:164494480:A:T	V476E	0.999
2:164494503:A:C	S468R	0.999
2:164494503:A:T	S468R	0.999
2:164494505:T:G	S468R	0.999
2:164494510:C:G	R466P	0.999
2:164497052:T:A	R446S	0.999
2:164497052:T:G	R446S	0.999
2:164497053:C:A	R446I	0.999
2:164497053:C:G	R446T	0.999
2:164508481:A:G	W333R	0.999
2:164508481:A:T	W333R	0.999
2:164522045:A:G	W251R	0.999
2:164522045:A:T	W251R	0.999
2:164493079:A:G	L527P	0.998
2:164493079:A:T	L527H	0.998
2:164493094:A:G	L522P	0.998

dbSNP variants (sampled 300 via entrez): RS1000034033 (2:164573215 GTC>G), RS1000048073 (2:164511115 C>T), RS1000070319 (2:164564266 T>C), RS1000081427 (2:164599586 G>C), RS1000100478 (2:164569143 G>A), RS1000121278 (2:164610891 C>A), RS1000148459 (2:164509154 G>A), RS1000181901 (2:164594486 T>C,G), RS1000187277 (2:164591405 A>T), RS1000199680 (2:164545987 AT>A), RS1000205192 (2:164583663 C>G), RS1000234092 (2:164594200 G>A), RS1000258993 (2:164539069 T>C), RS1000337901 (2:164536654 A>G), RS1000354839 (2:164525606 G>A)

Disease associations

OMIM: gene MIM:601524 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

175 associations (top):

Study	Trait	p-value
GCST000635_36	Response to statin therapy	6.000000e-06
GCST000829_13	Waist-hip ratio	2.000000e-24
GCST001072_4	Blood pressure	4.000000e-11
GCST001213_1	Type 2 diabetes	1.000000e-08
GCST001526_6	Fasting blood insulin (BMI interaction)	4.000000e-20
GCST002063_8	Sexual dimorphism in anthropometric traits	6.000000e-16
GCST002352_5	Type 2 diabetes	2.000000e-06
GCST002497_7	Blood pressure	2.000000e-06
GCST002782_81	Waist-to-hip ratio adjusted for body mass index	5.000000e-30
GCST002782_82	Waist-to-hip ratio adjusted for body mass index	6.000000e-15
GCST002782_83	Waist-to-hip ratio adjusted for body mass index	2.000000e-31
GCST002782_84	Waist-to-hip ratio adjusted for body mass index	4.000000e-16
GCST003139_2	Glomerular filtration rate in chronic kidney disease	2.000000e-06
GCST003272_8	Systolic blood pressure	3.000000e-08
GCST003435_13	Body fat percentage	2.000000e-06
GCST003435_19	Body fat percentage	2.000000e-08
GCST003435_34	Body fat percentage	5.000000e-06
GCST003435_5	Body fat percentage	6.000000e-09
GCST004063_76	Waist circumference adjusted for body mass index	4.000000e-15
GCST004064_12	Waist-hip ratio	1.000000e-23
GCST004064_76	Waist-hip ratio	3.000000e-09
GCST004066_139	Hip circumference	2.000000e-07
GCST004066_74	Hip circumference	2.000000e-09
GCST004067_202	Hip circumference adjusted for BMI	1.000000e-11
GCST004067_55	Hip circumference adjusted for BMI	1.000000e-10
GCST004279_4	Systolic blood pressure	1.000000e-11
GCST004500_68	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	9.000000e-14
GCST004501_55	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	1.000000e-13
GCST004504_53	Waist circumference adjusted for BMI in non-smokers	3.000000e-12
GCST004505_58	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	5.000000e-11

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0006335	systolic blood pressure
EFO:0004340	body mass index
EFO:0005951	sexual dimorphism
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007800	body fat percentage
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:1000965	Henoch-Schoenlein purpura
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0006340	mean arterial pressure
EFO:0004329	alcohol drinking
EFO:0006527	smoking status measurement
EFO:0008579	risk-taking behaviour
EFO:0009767	glycine measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	8
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	5
Cyclosporine	decreases expression	3
bisphenol A	affects cotreatment, increases expression, affects expression	2
sodium arsenite	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Nickel	decreases expression	2
Quercetin	decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Particulate Matter	affects response to substance, increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects response to substance, increases abundance	1
Arsenic	affects methylation	1

Clinical trials (associated diseases)

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