FHOD1

Summary

FHOD1 (formin homology 2 domain containing 1, HGNC:17905) is a protein-coding gene on chromosome 16q22.1, encoding FH1/FH2 domain-containing protein 1 (Q9Y613). Required for the assembly of F-actin structures, such as stress fibers.

This gene encodes a protein which is a member of the formin/diaphanous family of proteins. The gene is ubiquitously expressed but is found in abundance in the spleen. The encoded protein has sequence homology to diaphanous and formin proteins within the Formin Homology (FH)1 and FH2 domains. It also contains a coiled-coil domain, a collagen-like domain, two nuclear localization signals, and several potential PKC and PKA phosphorylation sites. It is a predominantly cytoplasmic protein and is expressed in a variety of human cell lines. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 29109 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 221 total
• MANE Select transcript: NM_013241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17905
Approved symbol	FHOD1
Name	formin homology 2 domain containing 1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FHOS
Ensembl gene	ENSG00000135723
Ensembl biotype	protein_coding
OMIM	606881
Entrez	29109

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 17 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000258201, ENST00000561922, ENST00000562266, ENST00000566006, ENST00000567509, ENST00000567561, ENST00000567752, ENST00000568595, ENST00000569085, ENST00000569888, ENST00000910035, ENST00000910036, ENST00000910037, ENST00000910038, ENST00000910039, ENST00000910040, ENST00000910041, ENST00000910042, ENST00000910043, ENST00000910044, ENST00000910045, ENST00000932112, ENST00000932113, ENST00000932114, ENST00000966997, ENST00000966998

RefSeq mRNA: 2 — MANE Select: NM_013241 NM_001318202, NM_013241

CCDS: CCDS10834

Canonical transcript exons

ENST00000258201 — 22 exons

Exon	Start	End
ENSE00001597166	67238380	67238447
ENSE00001678376	67238202	67238307
ENSE00001681391	67238903	67238967
ENSE00001907314	67247210	67247481
ENSE00001938044	67229389	67229718
ENSE00003468299	67237475	67237569
ENSE00003476358	67232039	67232194
ENSE00003492723	67230066	67230228
ENSE00003522875	67231637	67231819
ENSE00003524573	67236557	67236733
ENSE00003534170	67230601	67230791
ENSE00003583291	67234357	67234472
ENSE00003602882	67237239	67237382
ENSE00003608422	67237657	67237768
ENSE00003611038	67229793	67229990
ENSE00003611924	67231430	67231549
ENSE00003637109	67233657	67234267
ENSE00003646990	67230314	67230506
ENSE00003647501	67239348	67239454
ENSE00003654854	67238034	67238128
ENSE00003659925	67236966	67237114
ENSE00003668167	67231188	67231349

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 97.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7568 / max 410.9155, expressed in 1796 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157757	15.7532	1777
157758	1.4293	867
157754	0.3299	161
157755	0.2445	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	97.89	gold quality
gastrocnemius	UBERON:0001388	97.09	gold quality
upper lobe of left lung	UBERON:0008952	96.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.77	gold quality
muscle of leg	UBERON:0001383	96.52	gold quality
right lung	UBERON:0002167	96.48	gold quality
apex of heart	UBERON:0002098	96.42	gold quality
upper lobe of lung	UBERON:0008948	96.06	gold quality
muscle organ	UBERON:0001630	95.60	gold quality
granulocyte	CL:0000094	95.39	gold quality
right lobe of thyroid gland	UBERON:0001119	95.19	gold quality
gluteal muscle	UBERON:0002000	95.06	gold quality
right adrenal gland cortex	UBERON:0035827	94.71	gold quality
right adrenal gland	UBERON:0001233	94.41	gold quality
triceps brachii	UBERON:0001509	94.33	gold quality
right ovary	UBERON:0002118	94.29	gold quality
left lobe of thyroid gland	UBERON:0001120	94.28	gold quality
left adrenal gland cortex	UBERON:0035825	93.79	gold quality
left adrenal gland	UBERON:0001234	93.72	gold quality
stromal cell of endometrium	CL:0002255	93.47	gold quality
vastus lateralis	UBERON:0001379	93.45	gold quality
quadriceps femoris	UBERON:0001377	93.24	gold quality
omental fat pad	UBERON:0010414	93.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.09	gold quality
peritoneum	UBERON:0002358	93.07	gold quality
skeletal muscle tissue	UBERON:0001134	93.05	gold quality
metanephros cortex	UBERON:0010533	92.90	gold quality
mucosa of transverse colon	UBERON:0004991	92.71	gold quality
thyroid gland	UBERON:0002046	92.69	gold quality
right atrium auricular region	UBERON:0006631	92.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting FHOD1, 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-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-3139	96.68	66.77	652
HSA-MIR-28-5P	96.16	66.12	579
HSA-MIR-708-5P	96.16	66.12	576
HSA-MIR-4497	92.25	64.06	134

Literature-anchored findings (GeneRIF, showing 30)

• FHOS mediates an interaction between GLUT4/IRAP (insulin-responsive aminopeptidase) -containing vesicles and the cytoskeleton and may participate in exocytosis and/or retention of this membrane compartment (PMID:12677009)
• Fhos directly binds to F-actin via the N-terminal region, forms a homotypic complex via the FH2 domain to organize actin cytoskeleton (PMID:14576350)
• FHOD1 has a role in cyclic GMP-dependent inhibition of vascular smooth muscle cell stress fiber formation and/or migration (PMID:15051728)
• Oligomerization of FHOD1 via the coiled-coil motif is a critical parameter for its biological activities. (PMID:15642356)
• Sustained cell elongation is a consequence of FHOD1-mediated actin-microtubule coordination. (PMID:15878344)
• These novel data demonstrate that FHOD1-ERK MAP kinase interaction regulates key aspects of FHOD1 biology. (PMID:16112087)
• in FHOD1, DAD acts as signal sequence for binding to the well folded and monomeric FH3 domain (PMID:16361249)
• This study demonstrates FHOD1 is cleaved by caspase-3 at the SVPD(616) site during apoptosis and the C-terminal FHOD1 cleavage product has the ability to inhibit RNA polymerase I transcription. (PMID:17013756)
• In this study, the N-terminal region (residues 1-339) of the human formin homology domain-containing protein 1 (FHOD1) was purified and crystallized. (PMID:17909294)
• FHOD1 is activated through phosphorylation by rho-dependent protein kinase (ROCK)and has an important function in stress fibre formation in vascular endothelial cells (PMID:18239683)
• The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing. (PMID:18694941)
• Mutation of one residue in the predicted DAD-interaction surface efficiently activates FHOD1 in cells. (PMID:18786395)
• FHOD1 is a critical regulator of smooth muscle cell phenotype and is regulated by ROCK-dependent phosphorylation. (PMID:21106951)
• Letter: G-protein coupled and ITAM receptor regulation of the formin FHOD1 through Rho kinase in platelets. (PMID:21605332)
• FHOD1 and PPM1F (direct regulators of the actin cytoskeleton) were identified as novel targets of miR-200c. Expression levels of FHOD1 and PPM1F were inversely correlated with miR-200c level in breast cancer cell lines and breast cancer patient samples. (PMID:22144583)
• SIRPalpha/CD172a and FHOD1 are unique markers of littoral cells, a recently evolved major cell population of red pulp of human spleen. (PMID:22490440)
• FHOD1 stabilizes actin filaments by protecting barbed ends from depolymerization with its dimeric FH2 domain, whereas the region N-terminal to the FH1 domain mediates F-actin bundling by simultaneously binding to the sides of adjacent F-actin filaments. (PMID:23444374)
• Cdh1 contributes to spatiotemporal organization of AurB activity, and organization of FHOD1 activity by AurB contributes to daughter cell spreading after mitosis. (PMID:23613471)
• FHOD1 participates in cytoskeletal changes in epithelial-mesenchymal transition. (PMID:24086398)
• FHOD1 promotes formation of short actin filaments and transiently associates with transverse arcs providing tight temporal and spatial control of the formation and turnover of transverse arcs into mature ventral stress fibers during dynamic cell behavior. (PMID:24481812)
• the diaphanous formin FHOD1 as an interaction partner of N2G (PMID:24880667)
• Report FODH1 expression in cardiomyocytes and increased expression in dilated cardiommyopathy. (PMID:25125170)
• Immunostaining of sections of hearts with both anti-FHOD1 antibodies confirmed the presence of FHOD1 in intercalated discs and double immunostaining demonstrated its colocalisation with cadherin, plakoglobin and shifted localization to connexin43. (PMID:25555464)
• FHOD1 and INF2 are novel regulators of inter- and intra-structural contractility of podosomes. (PMID:26621033)
• results suggest that FHOD1 participates in key cellular processes that are dysregulated in malignancy (PMID:27919746)
• The functional integrity of lamin and nesprin-1 is thus required to modulate the FHOD1 activity and the inside-out mechanical coupling that tunes the cell internal stiffness to match that of its soft, physiological-like environment. (PMID:28455503)
• FHOD1 plays a critical role in the spatial and temporal coordination of cellular stress fiber dynamics without disrupting the formation of stress fiber networks. (PMID:31657439)
• Multiple formin proteins participate in glioblastoma migration. (PMID:32727404)
• Structures of FHOD1-Nesprin1/2 complexes reveal alternate binding modes for the FH3 domain of formins. (PMID:33472039)
• FHOD1 is upregulated in glioma cells and attenuates ferroptosis of glioma cells by targeting HSPB1 signaling. (PMID:37211949)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhod1	ENSDARG00000051768
mus_musculus	Fhod1	ENSMUSG00000014778
rattus_norvegicus	Fhod1	ENSRNOG00000054625
drosophila_melanogaster	Frl	FBGN0267795
caenorhabditis_elegans	fhod-1	WBGENE00016735
caenorhabditis_elegans		WBGENE00018976
caenorhabditis_elegans		WBGENE00019030
caenorhabditis_elegans	sydn-1	WBGENE00021473
caenorhabditis_elegans		WBGENE00021698

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHDC1 (ENSG00000137460), DIAPH3 (ENSG00000139734), DAAM2 (ENSG00000146122), DIAPH2 (ENSG00000147202), FMN2 (ENSG00000155816), FMNL2 (ENSG00000157827), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485), GRID2IP (ENSG00000215045)

Protein

Protein identifiers

FH1/FH2 domain-containing protein 1 — Q9Y613 (reviewed: Q9Y613)

Alternative names: Formin homolog overexpressed in spleen 1, Formin homology 2 domain-containing protein 1

All UniProt accessions (6): A0A068F7M9, Q9Y613, H3BVE7, J3KT53, J3KTH7, J3QR24

UniProt curated annotations — full annotation on UniProt →

Function. Required for the assembly of F-actin structures, such as stress fibers. Depends on the Rho-ROCK cascade for its activity. Contributes to the coordination of microtubules with actin fibers and plays a role in cell elongation. Acts synergistically with ROCK1 to promote SRC-dependent non-apoptotic plasma membrane blebbing.

Subunit / interactions. Self-associates via the FH2 domain. Binds to F-actin via its N-terminus. Binds to the cytoplasmic domain of CD21 via its C-terminus. Interacts with ROCK1 in a Src-dependent manner.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Bleb.

Tissue specificity. Ubiquitous. Highly expressed in spleen.

Post-translational modifications. Phosphorylated by ROCK1.

Domain organisation. The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.

Similarity. Belongs to the formin homology family.

RefSeq proteins (2): NP_001305131, NP_037373* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR014768	GBD/FH3_dom	Domain
IPR015425	FH2_Formin	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR041387	FHOD1_GBD_N	Domain
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR056771	FH3_FHOD1-3-like	Domain

Pfam: PF02181, PF18382, PF24959

UniProt features (69 total): helix 21, sequence conflict 14, modified residue 7, compositionally biased region 6, strand 6, region of interest 5, domain 4, turn 3, initiator methionine 1, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3DAD	X-RAY DIFFRACTION	2.3
6XF1	X-RAY DIFFRACTION	2.8
6XF2	X-RAY DIFFRACTION	7.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y613-F1	69.59	0.29

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 (7): 367, 486, 495, 498, 523, 573, 690

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 176 (showing top): E2F_Q4, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, chr16q22, E2F4DP1_01, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, USF_C, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, E2F1DP1_01, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, E2F1DP2_01, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, NF1_Q6_01

GO Biological Process (6): actin filament organization (GO:0007015), nuclear migration (GO:0007097), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of stress fiber assembly (GO:0051492), positive regulation of stress fiber assembly (GO:0051496), establishment of centrosome localization (GO:0051660)

GO Molecular Function (4): identical protein binding (GO:0042802), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), intercalated disc (GO:0014704), membrane (GO:0016020), bleb (GO:0032059), stress fiber (GO:0001725), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
establishment of organelle localization	2
stress fiber assembly	2
actin cytoskeleton organization	1
supramolecular fiber organization	1
intracellular transport	1
nucleus localization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
regulation of actin filament bundle assembly	1
regulation of actomyosin structure organization	1
positive regulation of actin filament bundle assembly	1
regulation of stress fiber assembly	1
centrosome localization	1
establishment of localization in cell	1
protein binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
cell-cell contact zone	1
plasma membrane bounded cell projection	1
actomyosin	1
contractile actin filament bundle	1

Protein interactions and networks

STRING

836 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHOD1	SYNE2	Q8WXH0	928
FHOD1	SYNE1	Q8NF91	765
FHOD1	DES	P17661	695
FHOD1	TMEM201	Q5SNT2	634
FHOD1	PFN4	Q8NHR9	616
FHOD1	PPM1F	P49593	604
FHOD1	NES	P48681	597
FHOD1	FSCN1	Q16658	582
FHOD1	SPIRE1	Q08AE8	573
FHOD1	PFN3	P60673	556
FHOD1	PFN1	P07737	555
FHOD1	FMNL1	O95466	545
FHOD1	AKT1	P31749	540
FHOD1	FNBP4	Q8N3X1	524
FHOD1	TOR1A	O14656	522

IntAct

82 interactions, top by confidence:

A	B	Type	Score
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
FHOD1	FHOD1	psi-mi:“MI:0407”(direct interaction)	0.750
FHOD1	FHOD1	psi-mi:“MI:0915”(physical association)	0.750
FHOD1	SYNE2	psi-mi:“MI:0915”(physical association)	0.580
TRIM21	FHOD1	psi-mi:“MI:0915”(physical association)	0.560
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
SUOX	CES3	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
FHOD1	Syne2	psi-mi:“MI:0915”(physical association)	0.510
FHOD1	HRAS	psi-mi:“MI:0407”(direct interaction)	0.440
	DENR	psi-mi:“MI:0915”(physical association)	0.400
RAC1	FHOD1	psi-mi:“MI:0915”(physical association)	0.400
FHOD1	NLGN3	psi-mi:“MI:0915”(physical association)	0.370
FHOD1	CDC42	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (99): FHOD1 (Affinity Capture-MS), FHOD1 (Affinity Capture-MS), FHOD1 (Two-hybrid), FHOD1 (Affinity Capture-MS), GALE (Co-fractionation), FHOD1 (Two-hybrid), TARS (Co-fractionation), FHOD1 (Affinity Capture-MS), FHOD1 (Affinity Capture-MS), FHOD1 (Affinity Capture-MS), FHOD1 (Two-hybrid), FHOD1 (Affinity Capture-MS), FHOD1 (Affinity Capture-MS), FHOD1 (Affinity Capture-MS), FHOD1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JV04, B0V207, D3Z8X7, D3ZFJ3, D3ZND0, F1LM81, G9CGD6, O00499, O08539, O08839, O12940, O60308, O60784, O75674, O88746, P42567, P55194, Q05DH4, Q0GNC1, Q0IHV1, Q27J81, Q3B7M3, Q3UN70, Q4KLN4, Q505K2, Q5FVK6, Q5T0F9, Q5U3K5, Q66HA5, Q68EF0, Q6P1N0, Q6P5E6, Q6P9Q4, Q6P9Q6, Q80V31, Q80V94, Q8BMI3, Q8BRN9, Q8K1A6, Q8R0H9

Diamond homologs: A3AB67, Q2V2M9, Q6P9Q4, Q76LL6, Q9Y613

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PRKG1	up-regulates	FHOD1	phosphorylation
ROCK1	up-regulates	FHOD1	phosphorylation
FHOD1	“up-regulates quantity by stabilization”	ACTB	binding
SRC	“up-regulates activity”	FHOD1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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
Cargo trafficking to the periciliary membrane	5	20.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	192
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3561 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67229988:TGCCT:T	acceptor_loss	1.0000
16:67229991:C:CC	acceptor_gain	1.0000
16:67229991:CTGAG:C	acceptor_loss	1.0000
16:67230225:CTGT:C	acceptor_gain	1.0000
16:67230229:C:CC	acceptor_gain	1.0000
16:67230311:CACCT:C	donor_loss	1.0000
16:67230312:A:AC	donor_gain	1.0000
16:67230313:C:CC	donor_gain	1.0000
16:67230313:CCT:C	donor_gain	1.0000
16:67230507:C:CC	acceptor_gain	1.0000
16:67230507:C:CG	acceptor_loss	1.0000
16:67230512:C:CT	acceptor_gain	1.0000
16:67230517:C:CT	acceptor_gain	1.0000
16:67230518:A:T	acceptor_gain	1.0000
16:67230595:CCCTA:C	donor_loss	1.0000
16:67230596:CCTA:C	donor_loss	1.0000
16:67230597:CTAC:C	donor_loss	1.0000
16:67230598:TACCT:T	donor_loss	1.0000
16:67230600:C:A	donor_loss	1.0000
16:67230626:T:A	donor_gain	1.0000
16:67230632:G:C	donor_gain	1.0000
16:67230787:TCCAC:T	acceptor_gain	1.0000
16:67230788:CCAC:C	acceptor_gain	1.0000
16:67230788:CCACC:C	acceptor_gain	1.0000
16:67230789:CACC:C	acceptor_gain	1.0000
16:67230792:CTG:C	acceptor_loss	1.0000
16:67231426:TCAC:T	donor_loss	1.0000
16:67231427:CA:C	donor_loss	1.0000
16:67231796:C:CT	acceptor_gain	1.0000
16:67232033:CCTCA:C	donor_loss	1.0000

AlphaMissense

7453 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67238282:A:G	F156S	1.000
16:67231339:A:G	F839S	0.999
16:67237485:A:G	L280P	0.999
16:67237558:A:G	W256R	0.999
16:67237558:A:T	W256R	0.999
16:67237737:A:G	L225P	0.999
16:67238060:A:G	W206R	0.999
16:67238060:A:T	W206R	0.999
16:67238255:A:G	L165P	0.999
16:67238268:C:A	G161W	0.999
16:67238268:C:G	G161R	0.999
16:67238268:C:T	G161R	0.999
16:67238282:A:C	F156C	0.999
16:67238294:A:G	L152P	0.999
16:67238396:A:G	L142P	0.999
16:67238401:G:C	F140L	0.999
16:67238401:G:T	F140L	0.999
16:67238403:A:G	F140L	0.999
16:67238405:A:G	L139P	0.999
16:67238441:A:G	L127P	0.999
16:67229714:T:A	R1139S	0.998
16:67229714:T:G	R1139S	0.998
16:67230321:A:G	I1015T	0.998
16:67231338:A:C	F839L	0.998
16:67231338:A:T	F839L	0.998
16:67231340:A:G	F839L	0.998
16:67231672:A:G	W784R	0.998
16:67231672:A:T	W784R	0.998
16:67231815:A:G	L736P	0.998
16:67232058:A:T	V728D	0.998

dbSNP variants (sampled 300 via entrez): RS1000136785 (16:67243148 G>A), RS1000245770 (16:67249360 G>A), RS1000546607 (16:67241013 G>A,T), RS1000605423 (16:67246393 G>A), RS1000636007 (16:67242716 A>G), RS1000678201 (16:67247545 C>G,T), RS1001083234 (16:67246151 G>A), RS1001379415 (16:67236440 A>G), RS1001518103 (16:67247124 C>A,T), RS1001843256 (16:67245764 G>C), RS1002029167 (16:67246849 G>T), RS1002037606 (16:67248595 C>G,T), RS1002934047 (16:67232361 CAAA>C,CAA,CAAAA), RS1003109568 (16:67246072 T>C), RS1003154436 (16:67231016 G>A)

Disease associations

OMIM: gene MIM:606881 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90020029_569	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation	3
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
entinostat	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1

Clinical trials (associated diseases)

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