EHD3

Summary

EHD3 (EH domain containing 3, HGNC:3244) is a protein-coding gene on chromosome 2p23.1, encoding EH domain-containing protein 3 (Q9NZN3). ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis.

Predicted to enable nucleic acid binding activity. Involved in several processes, including cytosolic transport; endocytic recycling; and protein homooligomerization. Acts upstream of or within protein localization to plasma membrane and regulation of cardiac muscle cell membrane potential. Located in ciliary pocket membrane and recycling endosome membrane.

Source: NCBI Gene 30845 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_014600

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3244
Approved symbol	EHD3
Name	EH domain containing 3
Location	2p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000013016
Ensembl biotype	protein_coding
OMIM	605891
Entrez	30845

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000322054, ENST00000907586, ENST00000907587, ENST00000944864, ENST00000944865

RefSeq mRNA: 1 — MANE Select: NM_014600 NM_014600

CCDS: CCDS1774

Canonical transcript exons

ENST00000322054 — 6 exons

Exon	Start	End
ENSE00000739271	31260510	31260922
ENSE00000739275	31261549	31261713
ENSE00000809419	31234152	31234848
ENSE00000809421	31244274	31244450
ENSE00001282605	31266177	31269451
ENSE00001779111	31249371	31249468

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0918 / max 212.4673, expressed in 1553 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19618	7.6289	1269
19617	5.2535	1331
19616	1.1073	730
19614	0.7575	380
19615	0.3446	169

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	97.82	gold quality
postcentral gyrus	UBERON:0002581	95.63	gold quality
parietal lobe	UBERON:0001872	95.61	gold quality
orbitofrontal cortex	UBERON:0004167	95.61	gold quality
superior frontal gyrus	UBERON:0002661	95.50	gold quality
cerebellar vermis	UBERON:0004720	95.47	gold quality
dorsal root ganglion	UBERON:0000044	95.31	gold quality
middle temporal gyrus	UBERON:0002771	95.25	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.67	gold quality
lower esophagus mucosa	UBERON:0035834	94.34	gold quality
entorhinal cortex	UBERON:0002728	94.04	gold quality
prefrontal cortex	UBERON:0000451	93.89	gold quality
CA1 field of hippocampus	UBERON:0003881	93.86	gold quality
frontal cortex	UBERON:0001870	93.28	gold quality
occipital lobe	UBERON:0002021	92.77	gold quality
primary visual cortex	UBERON:0002436	92.62	gold quality
neocortex	UBERON:0001950	92.26	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.85	gold quality
cerebral cortex	UBERON:0000956	91.76	gold quality
substantia nigra pars compacta	UBERON:0001965	91.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.76	gold quality
pons	UBERON:0000988	91.61	gold quality
temporal lobe	UBERON:0001871	91.58	gold quality
cingulate cortex	UBERON:0003027	91.55	gold quality
anterior cingulate cortex	UBERON:0009835	91.54	gold quality
right frontal lobe	UBERON:0002810	91.49	gold quality
superior vestibular nucleus	UBERON:0007227	91.45	gold quality
Ammon’s horn	UBERON:0001954	91.18	gold quality
trigeminal ganglion	UBERON:0001675	91.14	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	1720.41
E-MTAB-8205	yes	355.49
E-GEOD-84465	yes	23.59
E-ANND-3	yes	5.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting EHD3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
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-302C-5P	99.97	72.56	3642
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-4273	99.45	67.93	1206

Literature-anchored findings (GeneRIF, showing 13)

• EHD3: a protein that resides in recycling tubular and vesicular membrane structures and interacts with EHD1. (PMID:12121420)
• presented herein promote a coordinated role for EHD proteins and Rab11-FIP2 in mediating endocytic recycling and provide evidence for the function of EHD3 in early endosome to endocytic recycling compartment transport (PMID:16251358)
• Rab8a and Myosin Vb colocalize to a tubular network containing EHD1 and EHD3, which does not contain Rab11a. (PMID:17507647)
• Our findings support a role for EHD3 in regulating endosome-to-Golgi transport, and as a consequence, lysosomal biosynthetic, but not secretory, transport pathways are also affected (PMID:19139087)
• A new class of cardiac trafficking proteins(EHD1, EHD2, EHD3, EHD4) regulates cardiac membrane protein targeting. (PMID:20489164)
• The combined effect of the EHD3 and FREM3 genes may play an important role in developing major depressive disorder. (PMID:22337703)
• EHD3 is a previously unrecognized component of the cardiac remodeling pathway in heart failure. (PMID:22406195)
• evidence that the functions of both EHD1 and EHD4 are primarily in TRE membrane vesiculation, whereas EHD3 is a membrane-tubulating protein. (PMID:24019528)
• demonstrate Ehd3 growth inhibitory functions in glioma cells in vivo. We suggest that Ehd3 functions as a tumor suppressor gene and loss of its expression is a very common event in gliomas (PMID:24306026)
• 3 SNPs present in the EHD3 gene, of which rs619002 and rs644926 were exclusively associated with female major depressive disorder (PMID:24607927)
• The EHD3 gene may be associated with the endophenotype of cognitive function in major depressive disorder patients. (PMID:24997812)
• the residues Ala-519/Asp-520 of EHD1 and Asn-519/Glu-520 of EHD3 as defining the selectivity of these two paralogs for NPF-containing binding partners (PMID:27189942)
• Data provide evidence that EHD3 might undergo its tumor suppressor functions at least in part through promoting the sorting of activated EGFR to the lysosomal degradative compartment and spatio-temporal regulation of EGFR signaling via ERK and AKT. (PMID:27811356)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ehd3	ENSDARG00000007869
mus_musculus	Ehd3	ENSMUSG00000024065
rattus_norvegicus	Ehd3	ENSRNOG00000007744
drosophila_melanogaster	Dap160	FBGN0023388
drosophila_melanogaster	Eps-15	FBGN0035060
caenorhabditis_elegans		WBGENE00001224
caenorhabditis_elegans		WBGENE00006405

Paralogs (10): EHD2 (ENSG00000024422), EPS15 (ENSG00000085832), EHD4 (ENSG00000103966), EHD1 (ENSG00000110047), EPS15L1 (ENSG00000127527), REPS1 (ENSG00000135597), REPS2 (ENSG00000169891), SRL (ENSG00000185739), ITSN2 (ENSG00000198399), ITSN1 (ENSG00000205726)

Protein

Protein identifiers

EH domain-containing protein 3 — Q9NZN3 (reviewed: Q9NZN3)

Alternative names: PAST homolog 3

All UniProt accessions (1): Q9NZN3

UniProt curated annotations — full annotation on UniProt →

Function. ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis. In vitro causes tubulation of endocytic membranes. Binding to phosphatidic acid induces its membrane tubulation activity. Plays a role in endocytic transport. Involved in early endosome to recycling endosome compartment (ERC), retrograde early endosome to Golgi, and endosome to plasma membrane (rapid recycling) protein transport. Involved in the regulation of Golgi maintenance and morphology. Involved in the recycling of internalized D1 dopamine receptor. Plays a role in cardiac protein trafficking probably implicating ANK2. Involved in the ventricular membrane targeting of SLC8A1 and CACNA1C and probably the atrial membrane localization of CACNA1GG and CACNA1H implicated in the regulation of atrial myocyte excitability and cardiac conduction. In conjunction with EHD4 may be involved in endocytic trafficking of KDR/VEGFR2 implicated in control of glomerular function. Involved in the rapid recycling of integrin beta-3 implicated in cell adhesion maintenance. Involved in the unidirectional retrograde dendritic transport of endocytosed BACE1 and in efficient sorting of BACE1 to axons implicating a function in neuronal APP processing. Plays a role in the formation of the ciliary vesicle, an early step in cilium biogenesis; possibly sharing redundant functions with EHD1.

Subunit / interactions. Homooligomer, and heterooligomer with EHD1, EHD2 and EHD4, ATP-binding is required for heterooligomerization. Interacts with PACSIN1. Interacts with PACSIN2. Interacts (via EH domain) with MICALL1. Interacts (via EH domain) with RAB11FIP2. Interacts with ANK2.

Subcellular location. Recycling endosome membrane. Cell membrane. Cell projection. Cilium membrane.

Tissue specificity. Highly expressed in heart and brain and moderately expressed in kidney, liver, and placenta.

Domain organisation. The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.

Similarity. Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZN3-1	1	yes
Q9NZN3-2	2

RefSeq proteins (1): NP_055415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000261	EH_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030381	G_DYNAMIN_dom	Domain
IPR031692	EHD_N	Domain
IPR040990	DUF5600	Domain
IPR045063	Dynamin_N	Domain

Pfam: PF00350, PF12763, PF16880, PF18150

UniProt features (30 total): binding site 8, mutagenesis site 5, region of interest 5, domain 3, modified residue 3, cross-link 2, splice variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZN3-F1	88.56	0.68

Functional residue map

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

Ligand- & substrate-binding residues (8): 65–72; 220; 258; 489; 491; 493; 495; 500

Post-translational modifications (5): 1, 349, 456, 315, 511

Mutagenesis-validated functional residues (5):

Position	Phenotype
65	abolishes atp-binding and localizes to cytoplasm.
203	greatly reduces oligomerization and interaction with rab11fip2.
315	abolishes sumoylation and localization to tubular structures of the erc, impairs fast recycling activity from the erc, n
485	abolishes interaction with rab11fip2.
511	abolishes sumoylation localization to tubular structures of the erc, impairs fast recycling activity from the erc, no ef

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 268 (showing top): GOBP_REGULATION_OF_GOLGI_ORGANIZATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_LYSOSOMAL_TRANSPORT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GGGNRMNNYCAT_UNKNOWN, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, ATGTTAA_MIR302C, GOBP_REGULATION_OF_STRIATED_MUSCLE_CONTRACTION, VERNELL_RETINOBLASTOMA_PATHWAY_DN, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION

GO Biological Process (14): receptor recycling (GO:0001881), endocytosis (GO:0006897), protein transport (GO:0015031), endocytic recycling (GO:0032456), early endosome to Golgi transport (GO:0034498), protein homooligomerization (GO:0051260), regulation of cardiac muscle contraction (GO:0055117), cilium assembly (GO:0060271), protein localization to plasma membrane (GO:0072659), regulation of cardiac muscle cell membrane potential (GO:0086036), Golgi to lysosome transport (GO:0090160), regulation of Golgi organization (GO:1903358), regulation of cardiac conduction (GO:1903779), cell projection organization (GO:0030030)

GO Molecular Function (8): nucleic acid binding (GO:0003676), calcium ion binding (GO:0005509), ATP binding (GO:0005524), GTP binding (GO:0005525), protein-macromolecule adaptor activity (GO:0030674), nucleotide binding (GO:0000166), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (16): nucleus (GO:0005634), cytoplasm (GO:0005737), early endosome (GO:0005769), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), endosome membrane (GO:0010008), ciliary pocket membrane (GO:0020018), endocytic vesicle (GO:0030139), perinuclear region of cytoplasm (GO:0048471), recycling endosome membrane (GO:0055038), endosome (GO:0005768), cilium (GO:0005929), membrane (GO:0016020), cell projection (GO:0042995), ciliary membrane (GO:0060170)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of heart contraction	2
binding	2
purine ribonucleoside triphosphate binding	2
endosome	2
cytoplasm	2
bounding membrane of organelle	2
cytoplasmic vesicle	2
endocytosis	1
receptor metabolic process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
retrograde transport, endosome to Golgi	1
Golgi vesicle transport	1
protein complex oligomerization	1
regulation of striated muscle contraction	1
cardiac muscle contraction	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to membrane	1
protein localization to cell periphery	1
regulation of membrane potential	1
Golgi to vacuole transport	1
lysosomal transport	1
cytosolic transport	1
Golgi organization	1
regulation of organelle organization	1

Protein interactions and networks

STRING

1044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EHD3	EHBP1	Q8NDI1	981
EHD3	PACSIN2	Q9UNF0	838
EHD3	RAB11FIP2	Q7L804	837
EHD3	DYSF	O75923	831
EHD3	RBSN	Q9H1K0	776
EHD3	CAVIN1	Q6NZI2	769
EHD3	MYOF	Q9NZM1	711
EHD3	FER1L5	A0AVI2	683
EHD3	CAV1	Q03135	663
EHD3	DNM2	P50570	634
EHD3	PACSIN1	Q9BY11	632
EHD3	RAB10	P61026	626
EHD3	SLC2A4	P14672	587
EHD3	SNAP29	O95721	583
EHD3	MICALL1	Q8N3F8	581

IntAct

54 interactions, top by confidence:

A	B	Type	Score
EHD3	EHD1	psi-mi:“MI:0915”(physical association)	0.760
EHD3	EHD1	psi-mi:“MI:0403”(colocalization)	0.760
EHD3	MICALL1	psi-mi:“MI:0407”(direct interaction)	0.760
EHD3	MICALL1	psi-mi:“MI:0915”(physical association)	0.760
MICALL1	EHD3	psi-mi:“MI:0915”(physical association)	0.760
EHD1	EHD3	psi-mi:“MI:0915”(physical association)	0.760
RBSN	EHD3	psi-mi:“MI:0915”(physical association)	0.660
EHD2	EHD4	psi-mi:“MI:0914”(association)	0.640
ARL6IP1	EHD3	psi-mi:“MI:0915”(physical association)	0.560
ANK2	EHD3	psi-mi:“MI:0915”(physical association)	0.510
ANKFY1	EHD3	psi-mi:“MI:0915”(physical association)	0.510
EHD3	ANKFY1	psi-mi:“MI:0915”(physical association)	0.510
EHD3	Ehd3	psi-mi:“MI:0915”(physical association)	0.460
EHD3	Ehd3	psi-mi:“MI:0403”(colocalization)	0.460
INTU	PSMD12	psi-mi:“MI:0914”(association)	0.350
NUDCD1	APOBEC3B	psi-mi:“MI:0914”(association)	0.350
RBSN	LMX1B	psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
MICALL1	PLCG1	psi-mi:“MI:0914”(association)	0.350
EHD3	FERMT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): RAB11FIP2 (Two-hybrid), RAB11FIP2 (Affinity Capture-Western), RBSN (Two-hybrid), EHD3 (Two-hybrid), EHD1 (Two-hybrid), EHD3 (Two-hybrid), EHD3 (Co-fractionation), EHD3 (Affinity Capture-MS), EHD3 (Affinity Capture-MS), EHD3 (Affinity Capture-RNA), MICALL1 (Reconstituted Complex), MICALL1 (Two-hybrid), EHD3 (Proximity Label-MS), EHD1 (Two-hybrid), ARL6IP1 (Two-hybrid)

ESM2 similar proteins: A2VEI2, A8WQT4, B3MIF1, D6WIX5, O70200, P41044, P55008, P55009, P81076, Q02892, Q1LY46, Q21153, Q295E6, Q3UQ44, Q5E9G1, Q5E9R3, Q5RBP4, Q5TM25, Q5ZK33, Q641Z6, Q6AXZ3, Q6CM00, Q6DJ05, Q6FRV0, Q6GQ76, Q74ZK6, Q803R5, Q803V3, Q8CD10, Q8IQ70, Q8IYU8, Q8R491, Q94CF0, Q95PZ2, Q969Q6, Q99P77, Q9BDK2, Q9BZE4, Q9EQP2, Q9FEE2

Diamond homologs: A1CD74, A1CPG1, A1D2B8, A1DC51, A1DDY6, A2QRG2, A2R180, A3LN86, A3M008, A4R8N4, A5DF78, A5DP36, A5DVD6, A5DXI9, A6R7X5, A6RFP4, A6S9N4, A6SIJ6, A7E7N7, A7EKZ0, B0XR88, B0YC95, B2AS96, B2AWS3, L7IIY8, O42287, O54916, O94685, P0CT09, P32521, P42566, P42567, Q0CPW4, Q0D0N9, Q1DQC1, Q1DUU2, Q2H2V8, Q2H922, Q2UCH0, Q2UDY8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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 localization to plasma membrane	6	17.6×	3e-04
endocytosis	6	15.4×	3e-04
cilium assembly	5	9.9×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

865 predictions. Top by Δscore:

Variant	Effect	Δscore
2:31234849:G:A	donor_loss	1.0000
2:31244269:GCTA:G	acceptor_loss	1.0000
2:31244271:TA:T	acceptor_loss	1.0000
2:31244272:A:T	acceptor_loss	1.0000
2:31244447:ACAG:A	donor_gain	1.0000
2:31244451:G:GG	donor_gain	1.0000
2:31249466:GGG:G	donor_gain	1.0000
2:31249467:GG:G	donor_gain	1.0000
2:31249467:GGG:G	donor_gain	1.0000
2:31249468:GG:G	donor_gain	1.0000
2:31260920:AAGG:A	donor_loss	1.0000
2:31260921:AGGTG:A	donor_loss	1.0000
2:31260923:G:T	donor_loss	1.0000
2:31260924:T:G	donor_loss	1.0000
2:31261547:A:AG	acceptor_gain	1.0000
2:31261548:G:GA	acceptor_loss	1.0000
2:31261548:G:GG	acceptor_gain	1.0000
2:31261707:G:GT	donor_gain	1.0000
2:31266174:CA:C	acceptor_loss	1.0000
2:31234813:GGGCC:G	donor_gain	0.9900
2:31234849:G:GG	donor_gain	0.9900
2:31244268:T:TA	acceptor_gain	0.9900
2:31244272:A:AG	acceptor_gain	0.9900
2:31244273:G:GG	acceptor_gain	0.9900
2:31244446:AACAG:A	donor_gain	0.9900
2:31244448:CAG:C	donor_gain	0.9900
2:31244448:CAGGT:C	donor_gain	0.9900
2:31244449:AG:A	donor_gain	0.9900
2:31244449:AGG:A	donor_gain	0.9900
2:31244450:GG:G	donor_gain	0.9900

AlphaMissense

3564 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:31234806:T:C	L62P	1.000
2:31234814:G:C	G65R	1.000
2:31234815:G:A	G65D	1.000
2:31234820:T:C	Y67H	1.000
2:31234823:T:C	S68P	1.000
2:31234824:C:T	S68F	1.000
2:31234829:G:A	G70R	1.000
2:31234829:G:C	G70R	1.000
2:31234829:G:T	G70W	1.000
2:31234830:G:A	G70E	1.000
2:31234830:G:T	G70V	1.000
2:31234832:A:C	K71Q	1.000
2:31234836:C:T	T72I	1.000
2:31244312:G:A	G89E	1.000
2:31244320:C:T	P92S	1.000
2:31244321:C:A	P92H	1.000
2:31244377:G:A	G111R	1.000
2:31244377:G:C	G111R	1.000
2:31244377:G:T	G111W	1.000
2:31244378:G:A	G111E	1.000
2:31244378:G:T	G111V	1.000
2:31244384:C:A	A113D	1.000
2:31244387:T:C	L114P	1.000
2:31244432:G:T	G129V	1.000
2:31249423:G:C	D153H	1.000
2:31249430:C:A	P155Q	1.000
2:31249432:G:A	G156R	1.000
2:31249432:G:C	G156R	1.000
2:31249432:G:T	G156W	1.000
2:31249433:G:A	G156E	1.000

dbSNP variants (sampled 300 via entrez): RS1000258209 (2:31257019 A>G), RS1000453076 (2:31241932 C>G), RS1000512530 (2:31246190 A>C), RS1000542326 (2:31253197 A>G), RS1000719023 (2:31252190 T>A,C,G), RS1000850270 (2:31236098 T>C), RS1000860875 (2:31253456 G>A,T), RS1000923672 (2:31257427 G>A), RS1000933411 (2:31247764 C>G,T), RS1001087289 (2:31263070 G>A,C), RS1001147050 (2:31252089 G>A), RS1001278805 (2:31237280 A>G), RS1001314899 (2:31263696 T>C), RS1001508859 (2:31267873 C>T), RS1001532699 (2:31258181 G>A)

Disease associations

OMIM: gene MIM:605891 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST000497_11	Mean platelet volume	3.000000e-11
GCST001335_8	Mean platelet volume	1.000000e-12
GCST001337_7	Platelet count	9.000000e-14
GCST001553_5	Estradiol levels	5.000000e-07
GCST002184_8	Mean platelet volume	4.000000e-06
GCST004599_271	Mean platelet volume	8.000000e-109
GCST004603_206	Platelet count	9.000000e-73
GCST004607_214	Plateletcrit	1.000000e-18
GCST004611_10	High light scatter reticulocyte count	3.000000e-09
GCST004612_167	High light scatter reticulocyte percentage of red cells	6.000000e-11
GCST004616_127	Platelet distribution width	9.000000e-15
GCST004616_128	Platelet distribution width	2.000000e-225
GCST004619_159	Reticulocyte fraction of red cells	9.000000e-11
GCST006661_245	Male-pattern baldness	3.000000e-24
GCST009391_180	Metabolite levels	7.000000e-06
GCST90002385_124	High light scatter reticulocyte count	4.000000e-14
GCST90002386_242	High light scatter reticulocyte percentage of red cells	1.000000e-16
GCST90002389_106	Lymphocyte percentage of white cells	5.000000e-15
GCST90002389_107	Lymphocyte percentage of white cells	3.000000e-12
GCST90002393_181	Monocyte count	3.000000e-14
GCST90002393_182	Monocyte count	6.000000e-17
GCST90002393_183	Monocyte count	4.000000e-23
GCST90002395_523	Mean platelet volume	2.000000e-236
GCST90002395_524	Mean platelet volume	2.000000e-29
GCST90002398_331	Neutrophil count	8.000000e-12
GCST90002398_332	Neutrophil count	4.000000e-12
GCST90002398_333	Neutrophil count	2.000000e-10
GCST90002400_560	Plateletcrit	2.000000e-40
GCST90002401_371	Platelet distribution width	0.000000e+00
GCST90002401_372	Platelet distribution width	4.000000e-50

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004697	estradiol measurement
EFO:0007985	platelet crit
EFO:0007986	reticulocyte count
EFO:0007984	platelet component distribution width
EFO:0010476	dimethylglycine measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	5
sodium arsenite	increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-phenylbutyric acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Decitabine	affects cotreatment, affects expression	1
Vorinostat	affects cotreatment, affects expression	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Furaldehyde	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methylcholanthrene	affects binding, increases reaction	1
Smoke	decreases expression	1
Sodium Chloride	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Vanadates	increases expression	1

Clinical trials (associated diseases)

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