FHDC1

Summary

FHDC1 (FH2 domain containing 1, HGNC:29363) is a protein-coding gene on chromosome 4q31.3, encoding FH2 domain-containing protein 1 (Q9C0D6). Microtubule-associated formin which regulates both actin and microtubule dynamics.

Predicted to enable actin binding activity and microtubule binding activity. Involved in Golgi ribbon formation; cilium assembly; and stress fiber assembly. Located in cilium and microtubule.

Source: NCBI Gene 85462 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 224 total
• MANE Select transcript: NM_001371116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29363
Approved symbol	FHDC1
Name	FH2 domain containing 1
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1727, INF1
Ensembl gene	ENSG00000137460
Ensembl biotype	protein_coding
OMIM	620268
Entrez	85462

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000511601, ENST00000876678, ENST00000876679, ENST00000937747, ENST00000937748, ENST00000942461

RefSeq mRNA: 2 — MANE Select: NM_001371116 NM_001371116, NM_033393

CCDS: CCDS34081

Canonical transcript exons

ENST00000511601 — 12 exons

Exon	Start	End
ENSE00001002601	152960744	152960844
ENSE00001002602	152962814	152962884
ENSE00001002603	152963023	152963130
ENSE00001002608	152960565	152960650
ENSE00001081849	152953499	152953560
ENSE00001081850	152972377	152972541
ENSE00001081851	152964905	152964975
ENSE00001081852	152967980	152968097
ENSE00001081854	152954217	152954319
ENSE00002045627	152936323	152936409
ENSE00002053638	152942928	152943555
ENSE00002055797	152974675	152979671

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 92.82.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1168 / max 116.9630, expressed in 583 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50039	1.8690	542
50038	0.2478	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	92.82	gold quality
trabecular bone tissue	UBERON:0002483	90.77	gold quality
placenta	UBERON:0001987	89.01	gold quality
upper arm skin	UBERON:0004263	88.82	silver quality
pancreatic ductal cell	CL:0002079	85.81	gold quality
upper leg skin	UBERON:0004262	84.41	gold quality
tibia	UBERON:0000979	83.72	gold quality
epithelium of nasopharynx	UBERON:0001951	83.63	silver quality
esophagus squamous epithelium	UBERON:0006920	82.26	gold quality
gingival epithelium	UBERON:0001949	82.25	silver quality
endothelial cell	CL:0000115	82.04	silver quality
lower lobe of lung	UBERON:0008949	81.47	gold quality
oral cavity	UBERON:0000167	81.15	gold quality
gingiva	UBERON:0001828	81.13	silver quality
colonic mucosa	UBERON:0000317	80.26	gold quality
palpebral conjunctiva	UBERON:0001812	79.76	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.09	gold quality
amniotic fluid	UBERON:0000173	79.06	gold quality
thyroid gland	UBERON:0002046	79.02	gold quality
skin of leg	UBERON:0001511	78.80	gold quality
bone marrow	UBERON:0002371	78.29	gold quality
zone of skin	UBERON:0000014	78.23	gold quality
germinal epithelium of ovary	UBERON:0001304	78.19	silver quality
right lobe of thyroid gland	UBERON:0001119	78.13	gold quality
lower esophagus mucosa	UBERON:0035834	78.04	gold quality
left lobe of thyroid gland	UBERON:0001120	77.90	gold quality
skin of abdomen	UBERON:0001416	77.81	gold quality
ganglionic eminence	UBERON:0004023	77.77	gold quality
jejunal mucosa	UBERON:0000399	77.58	gold quality
mucosa of transverse colon	UBERON:0004991	77.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	83.46
E-ANND-3	yes	15.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting FHDC1, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540

Literature-anchored findings (GeneRIF, showing 1)

• LncRNA LINC00665 Promotes Ovarian Cancer Cell Proliferation and Inhibits Apoptosis via Targeting miR-181a-5p/FHDC. (PMID:35524876)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhdc1	ENSDARG00000074812
danio_rerio	fhdc5	ENSDARG00000095962
mus_musculus	Fhdc1	ENSMUSG00000041842
rattus_norvegicus	Fhdc1	ENSRNOG00000024594
caenorhabditis_elegans	fhod-1	WBGENE00016735
caenorhabditis_elegans		WBGENE00018976
caenorhabditis_elegans		WBGENE00019030
caenorhabditis_elegans	sydn-1	WBGENE00021473

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), 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

FH2 domain-containing protein 1 — Q9C0D6 (reviewed: Q9C0D6)

Alternative names: Inverted formin-1

All UniProt accessions (1): Q9C0D6

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-associated formin which regulates both actin and microtubule dynamics. Induces microtubule acetylation and stabilization and actin stress fiber formation. Regulates Golgi ribbon formation. Required for normal cilia assembly. Early in cilia assembly, may assist in the maturation and positioning of the centrosome/basal body, and once cilia assembly has initiated, may also promote cilia elongation by inhibiting disassembly.

Subunit / interactions. Interacts with CEP170.

Subcellular location. Cell projection. Cilium. Golgi apparatus.

Domain organisation. The FH2 and MBD domains are essential for its function in regulating Golgi ribbon formation.

RefSeq proteins (2): NP_001358045, NP_203751 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015425	FH2_Formin	Domain
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR051412	Formin_Homology_Diaphanous_sf	Family

Pfam: PF02181

UniProt features (24 total): compositionally biased region 11, modified residue 4, region of interest 4, sequence variant 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0D6-F1	58.63	0.26

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): 500, 650, 660, 664

Mutagenesis-validated functional residues (1):

Position	Phenotype
180	loss of actin-binding and ability to induce golgi ribbon formation. induces a significant increase in average cilia leng

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, RORA1_01, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, TGACCTY_ERR1_Q2, MARTINEZ_RB1_TARGETS_DN, GOBP_CILIUM_ORGANIZATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_GOLGI_RIBBON_FORMATION, GOMF_ACTIN_BINDING, GOBP_CELL_PROJECTION_ORGANIZATION, PTF1BETA_Q6, P53_DECAMER_Q2

GO Biological Process (5): actin filament polymerization (GO:0030041), stress fiber assembly (GO:0043149), cilium assembly (GO:0060271), Golgi ribbon formation (GO:0090161), cell projection organization (GO:0030030)

GO Molecular Function (2): actin binding (GO:0003779), microtubule binding (GO:0008017)

GO Cellular Component (6): Golgi apparatus (GO:0005794), microtubule (GO:0005874), cytoplasmic microtubule (GO:0005881), actin filament (GO:0005884), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
polymeric cytoskeletal fiber	2
actin polymerization or depolymerization	1
protein polymerization	1
contractile actin filament bundle assembly	1
actomyosin structure organization	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
Golgi organization	1
cellular component organization	1
cytoskeletal protein binding	1
tubulin binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
microtubule cytoskeleton	1
microtubule	1
actin cytoskeleton	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHDC1	RNF135	Q8IUD6	763
FHDC1	SSH2	Q76I76	682
FHDC1	SUZ12	Q15022	672
FHDC1	NUFIP1	Q9UHK0	668
FHDC1	EVI2B	P34910	650
FHDC1	EVI2A	P22794	639
FHDC1	PFN4	Q8NHR9	631
FHDC1	NF1	P21359	599
FHDC1	FNBP1	Q96RU3	542
FHDC1	PFN3	P60673	539
FHDC1	EMG1	Q92979	529
FHDC1	PRPF40A	O75400	518
FHDC1	PFN1	P07737	515
FHDC1	FMN2	Q9NZ56	502
FHDC1	ADAP2	Q9NPF8	493

IntAct

3 interactions, top by confidence:

A	B	Type	Score
FHDC1	EEF1D	psi-mi:“MI:0915”(physical association)	0.400
FHDC1	EEF1G	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): FHDC1 (Affinity Capture-RNA), FHDC1 (Proximity Label-MS), FHDC1 (Proximity Label-MS), FHDC1 (Affinity Capture-MS), HIST3H3 (Cross-Linking-MS (XL-MS)), FHDC1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8I3PDQ1, A5GFW5, E2RP94, M0R4F8, O35177, O70405, P59729, Q08EC4, Q14511, Q17R10, Q3UJB9, Q3ULW6, Q3ZAV8, Q4R8R1, Q5DTU0, Q5JV73, Q5PQS0, Q61140, Q63767, Q68CZ2, Q6A070, Q6IRU7, Q6P1H6, Q6P2E9, Q6P9J5, Q6PCQ0, Q6S5L8, Q6S5L9, Q6TXD4, Q6XZF7, Q7TNY7, Q7TP65, Q7TSI1, Q80TQ5, Q80VH0, Q8BW88, Q8C008, Q8C115, Q8IWE5, Q8K3I4

Diamond homologs: A2XUA1, A2YVG8, A3AB67, F1M775, O04532, O08808, O22824, O23373, O48682, O60610, P0C5K5, Q0D519, Q0D5P3, Q0DLG0, Q10Q99, Q54ER5, Q69MT2, Q6H7U3, Q6MWG9, Q6ZCX3, Q6ZKB2, Q7G6K7, Q7XUV2, Q7XWS7, Q84ZL0, Q8GX37, Q8H8K7, Q8S0F0, Q94B77, Q9C0D6, Q9FJX6, Q9FLQ7, Q9MA60, Q9SE97, Q9SK28, Q9SRR2, Q9XIE0, Q3ULZ2, Q9NSV4, Q24120

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	193
Likely benign	11
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2179 predictions. Top by Δscore:

Variant	Effect	Δscore
4:152953493:TTCCA:T	acceptor_loss	1.0000
4:152953494:TCCA:T	acceptor_loss	1.0000
4:152953495:CCA:C	acceptor_loss	1.0000
4:152953496:CA:C	acceptor_loss	1.0000
4:152953497:A:AG	acceptor_gain	1.0000
4:152953497:AGA:A	acceptor_loss	1.0000
4:152953498:G:GA	acceptor_loss	1.0000
4:152953498:G:GG	acceptor_gain	1.0000
4:152953558:G:GT	donor_gain	1.0000
4:152953558:GAA:G	donor_gain	1.0000
4:152953561:G:GG	donor_gain	1.0000
4:152954215:A:G	acceptor_gain	1.0000
4:152954315:AAGAG:A	donor_loss	1.0000
4:152954316:AGAG:A	donor_loss	1.0000
4:152954318:AG:A	donor_loss	1.0000
4:152954319:GGTA:G	donor_loss	1.0000
4:152954320:GTA:G	donor_loss	1.0000
4:152954321:T:G	donor_loss	1.0000
4:152960651:G:GG	donor_gain	1.0000
4:152960738:TTTCA:T	acceptor_loss	1.0000
4:152960739:TTCAG:T	acceptor_loss	1.0000
4:152960741:CAGC:C	acceptor_loss	1.0000
4:152960742:A:AG	acceptor_gain	1.0000
4:152960742:AGCT:A	acceptor_loss	1.0000
4:152960743:G:GG	acceptor_gain	1.0000
4:152960743:GC:G	acceptor_gain	1.0000
4:152960743:GCT:G	acceptor_gain	1.0000
4:152960743:GCTA:G	acceptor_gain	1.0000
4:152960743:GCTAT:G	acceptor_gain	1.0000
4:152960845:G:GA	donor_loss	1.0000

AlphaMissense

7436 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:152943361:T:A	W102R	0.998
4:152943361:T:C	W102R	0.998
4:152943363:G:C	W102C	0.997
4:152943363:G:T	W102C	0.997
4:152943406:T:A	W117R	0.997
4:152943406:T:C	W117R	0.997
4:152943408:G:C	W117C	0.996
4:152943408:G:T	W117C	0.996
4:152953539:T:C	I180T	0.996
4:152963050:T:C	F317L	0.996
4:152963051:T:C	F317S	0.996
4:152963052:T:A	F317L	0.996
4:152963052:T:G	F317L	0.996
4:152963123:T:A	V341D	0.996
4:152953518:A:T	K173I	0.995
4:152963111:T:C	L337P	0.995
4:152962859:T:C	L299P	0.994
4:152962864:G:C	A301P	0.994
4:152963048:G:A	G316E	0.994
4:152953519:A:C	K173N	0.993
4:152953519:A:T	K173N	0.993
4:152953545:T:C	L182P	0.993
4:152962872:T:A	N303K	0.993
4:152962872:T:G	N303K	0.993
4:152964908:G:C	A345P	0.993
4:152953539:T:A	I180K	0.992
4:152960575:T:C	L225S	0.992
4:152960763:G:C	A257P	0.992
4:152943469:T:C	F138L	0.991
4:152943471:T:A	F138L	0.991

dbSNP variants (sampled 300 via entrez): RS1000072036 (4:152942328 A>G,T), RS1000076524 (4:152948959 C>T), RS1000077679 (4:152936523 G>C), RS1000083430 (4:152914330 A>C), RS1000119070 (4:152956485 A>G), RS1000127757 (4:152943661 T>C), RS1000274111 (4:152916414 A>T), RS1000292505 (4:152973906 G>A), RS1000325170 (4:152929933 T>C), RS1000381314 (4:152923632 A>C), RS1000421971 (4:152942617 A>C,G), RS1000466125 (4:152948461 G>A), RS1000470001 (4:152930230 C>T), RS1000516220 (4:152948137 AC>A), RS1000641803 (4:152956926 C>T)

Disease associations

OMIM: gene MIM:620268 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000013_2	Amyotrophic lateral sclerosis	9.000000e-06
GCST001762_136	Obesity-related traits	8.000000e-06
GCST90002405_47	Reticulocyte count	3.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	increases methylation, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
tobacco tar	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
didecyldimethylammonium	decreases expression	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
cyanoginosin LR	decreases expression, increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	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
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Estradiol	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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