MICALL1

Summary

MICALL1 (MICAL like 1, HGNC:29804) is a protein-coding gene on chromosome 22q13.1, encoding MICAL-like protein 1 (Q8N3F8). Lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes.

Enables several functions, including identical protein binding activity; phosphatidic acid binding activity; and small GTPase binding activity. Involved in several processes, including plasma membrane tubulation; protein localization to organelle; and slow endocytic recycling. Located in centriole; cilium; and endosome.

Source: NCBI Gene 85377 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 182 total
• MANE Select transcript: NM_033386

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29804
Approved symbol	MICALL1
Name	MICAL like 1
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	MIRAB13, KIAA1668, MICAL-L1
Ensembl gene	ENSG00000100139
Ensembl biotype	protein_coding
OMIM	619563
Entrez	85377

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000215957, ENST00000402631, ENST00000424008, ENST00000445494, ENST00000454685, ENST00000489812, ENST00000679832, ENST00000680375, ENST00000680501, ENST00000680578, ENST00000680868, ENST00000681920, ENST00000869042, ENST00000869043, ENST00000869044, ENST00000919445

RefSeq mRNA: 4 — MANE Select: NM_033386 NM_001410818, NM_001410819, NM_001410820, NM_033386

CCDS: CCDS13961, CCDS93161, CCDS93162, CCDS93163

Canonical transcript exons

ENST00000215957 — 16 exons

Exon	Start	End
ENSE00000880234	37917707	37917795
ENSE00000936050	37924660	37924717
ENSE00001047864	37919036	37919178
ENSE00001047881	37925661	37926043
ENSE00001173236	37921972	37922426
ENSE00001938298	37940709	37942822
ENSE00001945112	37906297	37906568
ENSE00003627527	37912351	37912492
ENSE00003641254	37911952	37912000
ENSE00003666429	37927411	37927826
ENSE00003695379	37932798	37932888
ENSE00003696189	37932553	37932679
ENSE00003696313	37931799	37931933
ENSE00003697468	37933039	37933112
ENSE00003699394	37937746	37937792
ENSE00003700167	37937080	37937194

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 96.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.3483 / max 195.5355, expressed in 1814 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192218	18.0585	1797
192215	8.0862	1720
192216	0.8978	614
192214	0.8436	621
192217	0.1949	61
192221	0.1568	41
192220	0.1104	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	96.80	gold quality
gingival epithelium	UBERON:0001949	95.38	gold quality
sperm	CL:0000019	95.37	gold quality
gingiva	UBERON:0001828	93.99	gold quality
body of stomach	UBERON:0001161	93.57	gold quality
esophagus mucosa	UBERON:0002469	93.37	gold quality
squamous epithelium	UBERON:0006914	93.03	gold quality
hair follicle	UBERON:0002073	92.61	gold quality
placenta	UBERON:0001987	92.44	gold quality
lower esophagus mucosa	UBERON:0035834	92.30	gold quality
sural nerve	UBERON:0015488	92.05	gold quality
stomach	UBERON:0000945	91.85	gold quality
penis	UBERON:0000989	91.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.57	gold quality
male germ cell	CL:0000015	91.44	gold quality
skin of leg	UBERON:0001511	91.31	gold quality
mammalian vulva	UBERON:0000997	91.20	gold quality
esophagus	UBERON:0001043	91.11	gold quality
epithelium of esophagus	UBERON:0001976	91.09	gold quality
esophagus squamous epithelium	UBERON:0006920	91.07	gold quality
pancreatic ductal cell	CL:0002079	90.32	silver quality
fundus of stomach	UBERON:0001160	90.26	gold quality
skin of abdomen	UBERON:0001416	89.99	gold quality
parotid gland	UBERON:0001831	89.93	gold quality
zone of skin	UBERON:0000014	89.91	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.12	gold quality
stromal cell of endometrium	CL:0002255	88.96	gold quality
cervix epithelium	UBERON:0004801	88.90	gold quality
upper leg skin	UBERON:0004262	88.76	gold quality
lower esophagus	UBERON:0013473	88.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting MICALL1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-125A-5P	99.36	70.59	1640

Literature-anchored findings (GeneRIF, showing 13)

• These data implicate MICAL-L1 as an unusual type of Rab effector that regulates endocytic recycling by recruiting and linking EHD1 and Rab8a on membrane tubules. (PMID:19864458)
• novel insights into the MICAL-L1/Rab protein complex that can regulate EGFR trafficking at late endocytic pathways. (PMID:21795389)
• Rab35 is a critical upstream regulator of MICAL-L1 and Arf6, while both MICAL-L1 and Arf6 regulate Rab8a function. (PMID:21951725)
• Cooperation of MICAL-L1, pacsin 2 (syndapin2), and phosphatidic acid in tubular recycling endosome biogenesis. (PMID:23596323)
• MICAL-L1-mediated recruitment of EHD1 to Src-containing recycling endosomes is required for the release of Src from the perinuclear endocytic recycling compartment in response to growth factor stimulation. (PMID:24481818)
• DGKalpha generates phosphatidic acid to drive its own recruitment to tubular recycling endosomes via its interaction with MICAL-L1 (PMID:25248744)
• suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis (PMID:25287187)
• Findings found that ectopic expression of MICALL1 significantly inhibited the proliferation of HCT116 colorectal cancer cells. Also, MICALL1 expression was found to be suppressed in colorectal cancer with p53 mutations. (PMID:28714518)
• Data support the notion that a pool of centriolar gamma-tubulin and/or alpha-tubulin-beta-tubulin heterodimers anchor MICAL-L1 to the centriole, where it might recruit EHD1 to promote ciliogenesis. (PMID:31615969)
• Defining the protein and lipid constituents of tubular recycling endosomes. (PMID:33334886)
• A junctional PACSIN2/EHD4/MICAL-L1 complex coordinates VE-cadherin trafficking for endothelial migration and angiogenesis. (PMID:33972531)
• MICAL-L1 is required for cargo protein delivery to the cell surface. (PMID:34100897)
• Endosomal actin branching, fission, and receptor recycling require FCHSD2 recruitment by MICAL-L1. (PMID:39382837)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	micall1a	ENSDARG00000079811
mus_musculus	Micall1	ENSMUSG00000033039
rattus_norvegicus	Micall1	ENSRNOG00000026212
drosophila_melanogaster	MICAL-like	FBGN0036333

Paralogs (7): ASPM (ENSG00000066279), EHBP1 (ENSG00000115504), GAS2 (ENSG00000148935), MICALL2 (ENSG00000164877), EHBP1L1 (ENSG00000173442), GAS2L1 (ENSG00000185340), SMTNL1 (ENSG00000214872)

Protein

Protein identifiers

MICAL-like protein 1 — Q8N3F8 (reviewed: Q8N3F8)

Alternative names: Molecule interacting with Rab13

All UniProt accessions (9): Q8N3F8, A0A7P0T7Z5, A0A7P0T8A6, A0A7P0T9P2, A0A7P0Z427, A0A7P0Z4L3, B0QY86, B0QY91, H0Y6J8

UniProt curated annotations — full annotation on UniProt →

Function. Lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, acts as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation. Involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking. Alternatively, regulates slow endocytic recycling of endocytosed proteins back to the plasma membrane. Also involved in cargo protein delivery to the plasma membrane. Plays a role in ciliogenesis coordination, recruits EHD1 to primary cilium where it is anchored to the centriole through interaction with tubulins. May indirectly play a role in neurite outgrowth.

Subunit / interactions. Homooligomer. Interacts (via NPF1 motif) with EHD1 (via EH domain); the interaction is direct and probably recruits EHD1 to membranes. Interacts with EHD3 (via EH domain). Interacts with RAB35 (GTP-bound form); the interaction is direct and probably recruits MICALL1 to membranes. Interacts with ACAP2; the interaction is indirect through RAB35. Interacts with RAB8A (GTP-bound form); regulates RAB8A association with recycling endosomes. Interacts with RAB13 (GTP-bound form). Interacts with ARF6 (GTP-bound form). Interacts with PACSIN2 (via the SH3 domain). Interacts with DPYSL2.

Subcellular location. Recycling endosome membrane. Late endosome membrane. Cell projection. Cilium membrane. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Domain organisation. Probably exists in a closed and an opened conformation due to interaction of the C-terminal RAB-binding domain (RBD), also described as bivalent Mical/EHBP Rab binding (bMERB) domain, with the N-terminal calponin-homology (CH) domain. The conformational change is regulated by RAB13 and may modulate MICALL1 interactions with functional partners.

RefSeq proteins (4): NP_001397747, NP_001397748, NP_001397749, NP_203744* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR001781	Znf_LIM	Domain
IPR022735	bMERB_dom	Domain
IPR036872	CH_dom_sf	Homologous_superfamily
IPR050540	F-actin_Monoox_Mical	Family

Pfam: PF00307, PF00412, PF12130

UniProt features (49 total): modified residue 13, compositionally biased region 11, mutagenesis site 7, sequence variant 4, region of interest 4, domain 3, short sequence motif 2, sequence conflict 2, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KSP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3F8-F1	59.50	0.21

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 (13): 295, 309, 318, 391, 467, 469, 470, 471, 484, 486, 578, 621, 740

Mutagenesis-validated functional residues (7):

Position	Phenotype
385–387	no effect on interaction with pacsin2. loss of interaction with pacsin2; when associated with 480-a–a-483.
425–427	partial loss of interaction with ehd1. complete loss of interaction with ehd1; when associated with 633-a–a-635.
428–430	strongly reduces interaction with ehd1.
480–483	no effect on interaction with pacsin2. loss of interaction with pacsin2; when associated with 385-a–a-387.
633–635	no effect on interaction with ehd1. complete loss of interaction with ehd1; when associated with 425-a–a-427.
721–726	altered association with membranes.
742–743	loss of binding to phosphatidic acid and association with membrane tubules. no effect on interaction with rab8a and rab1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 228 (showing top): GCM_GSPT1, MODULE_255, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_PROTEIN_TARGETING, MODULE_317, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOCC_TRANS_GOLGI_NETWORK, GOBP_SPROUTING_ANGIOGENESIS

GO Biological Process (13): cell migration involved in sprouting angiogenesis (GO:0002042), protein targeting to membrane (GO:0006612), endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), protein transport (GO:0015031), neuron projection development (GO:0031175), endocytic recycling (GO:0032456), slow endocytic recycling (GO:0032458), protein localization to endosome (GO:0036010), cilium assembly (GO:0060271), protein localization to cilium (GO:0061512), plasma membrane tubulation (GO:0097320), plasma membrane bounded cell projection organization (GO:0120036)

GO Molecular Function (8): cytoskeletal adaptor activity (GO:0008093), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), cadherin binding (GO:0045296), metal ion binding (GO:0046872), phosphatidic acid binding (GO:0070300), protein binding (GO:0005515), protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (15): late endosome (GO:0005770), centriole (GO:0005814), adherens junction (GO:0005912), cilium (GO:0005929), cytoplasmic side of endosome membrane (GO:0010009), late endosome membrane (GO:0031902), recycling endosome membrane (GO:0055038), ciliary membrane (GO:0060170), cytoplasm (GO:0005737), endosome (GO:0005768), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995), recycling endosome (GO:0055037)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome membrane	3
cellular anatomical structure	3
protein localization to organelle	2
protein binding	2
endosome	2
intracellular membraneless organelle	2
sprouting angiogenesis	1
blood vessel endothelial cell migration	1
protein targeting	1
establishment of protein localization to membrane	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
endocytosis	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
neuron development	1
plasma membrane bounded cell projection organization	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
endocytic recycling	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
plasma membrane organization	1
cell projection organization	1
cytoskeletal protein binding	1
protein-macromolecule adaptor activity	1
GTPase binding	1
cell adhesion molecule binding	1
cation binding	1
phospholipid binding	1
anion binding	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MICALL1	EHD1	Q9H4M9	985
MICALL1	RAB13	P51153	797
MICALL1	RAB8A	P24407	778
MICALL1	RAB35	Q15286	767
MICALL1	PACSIN2	Q9UNF0	760
MICALL1	NEDD9	Q14511	725
MICALL1	RAB15	P59190	721
MICALL1	RAB10	P61026	686
MICALL1	RAB36	O95755	685
MICALL1	EPS15	P42566	673
MICALL1	EHD3	Q9NZN3	581
MICALL1	EHD4	Q9H223	520
MICALL1	ACAP2	Q15057	506
MICALL1	RAB11A	P24410	489
MICALL1	ARF6	P26438	489

IntAct

100 interactions, top by confidence:

A	B	Type	Score
YWHAG	MICALL1	psi-mi:“MI:0915”(physical association)	0.860
EHD1	MICALL1	psi-mi:“MI:0407”(direct interaction)	0.850
EHD1	MICALL1	psi-mi:“MI:0915”(physical association)	0.850
MICALL1	EHD1	psi-mi:“MI:0915”(physical association)	0.850
EHD1	MICALL1	psi-mi:“MI:0403”(colocalization)	0.850
EHD1	MICALL1	psi-mi:“MI:2364”(proximity)	0.850
YWHAB	MICALL1	psi-mi:“MI:0915”(physical association)	0.810
	RAB8A	psi-mi:“MI:0407”(direct interaction)	0.790
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
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600

BioGRID (128): EHD1 (Two-hybrid), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Proximity Label-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), KIF13B (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RR37, A1L170, A1L1I3, A1L260, A2AMM0, A4IFJ0, B5G1P1, D3ZQL6, E7F5E1, G5BQH4, O08919, O54724, O60237, O75420, P06759, P33622, P53814, P85125, Q2KI85, Q2TAL5, Q3T044, Q3UMT1, Q4RTJ5, Q4V882, Q5I1X5, Q5U2R6, Q63312, Q6NZI2, Q75AS0, Q80VC9, Q8BG95, Q8BGT6, Q8C0J6, Q8CI12, Q8IV56, Q8K382, Q8N3F8, Q8TEH3, Q8WUF5, Q91VJ2

Diamond homologs: A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O94851, O97592, P05094, P05095, P07751, P11277, P11530, P11531, P11532, P11533, P12814, P13395, P13466, P15508, P16086, P16546, P18091, P20111, P21333, P30427, P35609

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	5	61.4×	2e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	54.2×	2e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	54.2×	2e-06
Activation of BH3-only proteins	5	40.0×	7e-06
RHO GTPases activate PKNs	6	30.7×	3e-06
Intrinsic Pathway for Apoptosis	5	23.6×	6e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	17.4×	7e-06
Transcriptional and post-translational regulation of MITF-M expression and activity	6	17.3×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
endocytic recycling	7	26.4×	5e-06
protein targeting	5	25.8×	1e-04
protein localization to plasma membrane	9	13.8×	5e-06
cytoskeleton organization	7	13.1×	1e-04
intracellular protein localization	8	11.8×	8e-05
endocytosis	8	10.7×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	157
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2728 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37906564:CTGCT:C	donor_gain	1.0000
22:37906565:TGCT:T	donor_gain	1.0000
22:37906566:GCT:G	donor_gain	1.0000
22:37906566:GCTG:G	donor_gain	1.0000
22:37906569:G:GG	donor_gain	1.0000
22:37906569:G:T	donor_loss	1.0000
22:37906570:TGAG:T	donor_loss	1.0000
22:37906571:GAGT:G	donor_loss	1.0000
22:37911950:A:AG	acceptor_gain	1.0000
22:37911951:G:GG	acceptor_gain	1.0000
22:37911951:GA:G	acceptor_gain	1.0000
22:37911951:GAGA:G	acceptor_gain	1.0000
22:37911996:GTTTG:G	donor_gain	1.0000
22:37912000:GGTA:G	donor_loss	1.0000
22:37912001:G:GA	donor_loss	1.0000
22:37912001:G:GG	donor_gain	1.0000
22:37912002:T:A	donor_loss	1.0000
22:37912310:T:TA	acceptor_gain	1.0000
22:37912315:C:CA	acceptor_gain	1.0000
22:37912316:G:A	acceptor_gain	1.0000
22:37912319:T:A	acceptor_gain	1.0000
22:37912334:A:AG	acceptor_gain	1.0000
22:37912334:ACCT:A	acceptor_gain	1.0000
22:37912491:AGG:A	donor_loss	1.0000
22:37912492:GGT:G	donor_loss	1.0000
22:37912493:G:A	donor_loss	1.0000
22:37912494:T:G	donor_loss	1.0000
22:37919020:ACCTC:A	acceptor_gain	1.0000
22:37919035:GGGC:G	acceptor_gain	1.0000
22:37919174:TTCCG:T	donor_gain	1.0000

AlphaMissense

5597 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37906513:T:C	F31L	0.999
22:37906514:T:C	F31S	0.999
22:37906515:C:A	F31L	0.999
22:37906515:C:G	F31L	0.999
22:37906522:G:C	G34R	0.999
22:37906522:G:T	G34C	0.999
22:37906523:G:A	G34D	0.999
22:37906523:G:T	G34V	0.999
22:37906538:C:A	A39D	0.999
22:37912354:T:C	F67L	0.999
22:37912356:T:A	F67L	0.999
22:37912356:T:G	F67L	0.999
22:37912364:C:A	A70D	0.999
22:37912438:A:C	S95R	0.999
22:37912440:C:A	S95R	0.999
22:37912440:C:G	S95R	0.999
22:37932827:T:A	W725R	0.999
22:37932827:T:C	W725R	0.999
22:37932837:T:C	L728P	0.999
22:37933089:T:C	L762P	0.999
22:37937155:G:C	R795P	0.999
22:37906532:T:C	F37S	0.998
22:37906536:C:G	C38W	0.998
22:37911991:T:A	N62K	0.998
22:37911991:T:G	N62K	0.998
22:37911994:C:A	N63K	0.998
22:37911994:C:G	N63K	0.998
22:37912352:C:A	A66D	0.998
22:37912355:T:C	F67S	0.998
22:37912394:T:C	L80P	0.998

dbSNP variants (sampled 300 via entrez): RS1000094219 (22:37942534 C>T), RS1000172999 (22:37906290 T>C), RS1000242558 (22:37920220 TA>T,TAA), RS1000497339 (22:37921958 C>G), RS1000533392 (22:37911362 G>A,C), RS1000536695 (22:37937469 G>A), RS1000685968 (22:37904489 C>T), RS1000719884 (22:37932323 G>A), RS1000738808 (22:37933942 G>A,C,T), RS1000828434 (22:37928798 A>C,T), RS1000908252 (22:37940203 A>G), RS1001025653 (22:37905245 G>A), RS1001106894 (22:37923662 T>C), RS1001153894 (22:37934898 A>G), RS1001156663 (22:37911635 A>G)

Disease associations

OMIM: gene MIM:619563 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004616_175	Platelet distribution width	7.000000e-18
GCST006979_827	Heel bone mineral density	1.000000e-16
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10
GCST90002401_275	Platelet distribution width	1.000000e-18
GCST90002401_276	Platelet distribution width	1.000000e-51
GCST90002402_648	Platelet count	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0009270	heel bone mineral density
EFO:0004346	neuroimaging measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
methylmercuric chloride	increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	increases expression	3
Cyclosporine	increases expression	3
Aflatoxin B1	affects expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
deoxynivalenol	decreases phosphorylation	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
coumarin	affects phosphorylation	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	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
nutlin 3	affects cotreatment, increases expression, increases secretion	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1

Clinical trials (associated diseases)

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