FHIP2A

Summary

FHIP2A (FHF complex subunit HOOK interacting protein 2A, HGNC:29320) is a protein-coding gene on chromosome 10q25.3, encoding FHF complex subunit HOOK interacting protein 2A (Q5W0V3). Required for proper functioning of the nervous system.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 88 total — 1 likely-pathogenic
• MANE Select transcript: NM_020940

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29320
Approved symbol	FHIP2A
Name	FHF complex subunit HOOK interacting protein 2A
Location	10q25.3
Locus type	gene with protein product
Status	Approved
Aliases	bA106M7.3
Ensembl gene	ENSG00000151553
Ensembl biotype	protein_coding
OMIM	617312
Entrez	57700

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000369246, ENST00000369248, ENST00000369250, ENST00000411414, ENST00000710382

RefSeq mRNA: 2 — MANE Select: NM_020940 NM_001135051, NM_020940

CCDS: CCDS31290, CCDS44480

Canonical transcript exons

ENST00000369248 — 17 exons

Exon	Start	End
ENSE00001000272	114861231	114861334
ENSE00001000273	114847090	114847233
ENSE00001000274	114846559	114846728
ENSE00001000275	114848647	114848737
ENSE00001000276	114846013	114846089
ENSE00001000277	114842933	114843226
ENSE00001000278	114860749	114860889
ENSE00001000279	114861435	114864717
ENSE00001000280	114855197	114855340
ENSE00001000281	114846175	114846367
ENSE00001000282	114845367	114845481
ENSE00001000283	114843741	114843937
ENSE00001096971	114833233	114833402
ENSE00001096987	114835537	114835641
ENSE00001097005	114830852	114830930
ENSE00001097009	114836124	114836246
ENSE00003848175	114821780	114822123

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3285 / max 110.0044, expressed in 1782 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107168	13.0693	1781
107167	0.2592	112

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	98.30	gold quality
endothelial cell	CL:0000115	98.21	gold quality
oviduct epithelium	UBERON:0004804	96.92	gold quality
pancreatic ductal cell	CL:0002079	96.84	gold quality
tibialis anterior	UBERON:0001385	95.75	gold quality
middle temporal gyrus	UBERON:0002771	95.40	gold quality
sperm	CL:0000019	95.27	gold quality
tibia	UBERON:0000979	94.97	gold quality
visceral pleura	UBERON:0002401	94.93	gold quality
deltoid	UBERON:0001476	94.40	gold quality
parietal pleura	UBERON:0002400	94.36	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.01	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.98	gold quality
germinal epithelium of ovary	UBERON:0001304	93.71	gold quality
jejunal mucosa	UBERON:0000399	93.67	gold quality
left ventricle myocardium	UBERON:0006566	93.56	gold quality
cartilage tissue	UBERON:0002418	92.42	gold quality
ileal mucosa	UBERON:0000331	92.36	gold quality
placenta	UBERON:0001987	91.33	gold quality
skin of hip	UBERON:0001554	91.13	gold quality
decidua	UBERON:0002450	90.85	gold quality
cauda epididymis	UBERON:0004360	90.56	gold quality
bone marrow	UBERON:0002371	90.12	gold quality
myocardium	UBERON:0002349	90.10	gold quality
trabecular bone tissue	UBERON:0002483	89.88	gold quality
endometrium	UBERON:0001295	89.40	gold quality
seminal vesicle	UBERON:0000998	89.12	gold quality
calcaneal tendon	UBERON:0003701	88.85	gold quality
saphenous vein	UBERON:0007318	88.62	gold quality
layer of synovial tissue	UBERON:0007616	88.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

203 targeting FHIP2A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhip2a	ENSDARG00000060168
mus_musculus	Fhip2a	ENSMUSG00000033478
rattus_norvegicus	Fhip2a	ENSRNOG00000017225
drosophila_melanogaster	CG3558	FBGN0025681
caenorhabditis_elegans		WBGENE00015485

Paralogs (3): FHIP1B (ENSG00000051009), FHIP2B (ENSG00000158863), FHIP1A (ENSG00000164142)

Protein

Protein identifiers

FHF complex subunit HOOK interacting protein 2A — Q5W0V3 (reviewed: Q5W0V3)

All UniProt accessions (4): Q5W0V3, A0AA34QVS8, Q5W0V1, Q5W0V4

UniProt curated annotations — full annotation on UniProt →

Function. Required for proper functioning of the nervous system.

Tissue specificity. Expressed in all tissues tested, highly expressed brain. Only detected at high levels in testis.

Similarity. Belongs to the FHIP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5W0V3-1	1	yes
Q5W0V3-2	2

RefSeq proteins (2): NP_001128523, NP_065991* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019384	FHIP	Family
IPR045668	FHIP_KELAA_motif	Conserved_site
IPR045669	FHIP_C	Domain

Pfam: PF10257, PF19311, PF19314

UniProt features (13 total): sequence conflict 3, sequence variant 3, region of interest 2, compositionally biased region 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W0V3-F1	80.50	0.58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 169 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_LIVER_CANCER_UP, chr10q25, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, CAGCTTT_MIR320, BOCHKIS_FOXA2_TARGETS, LU_EZH2_TARGETS_DN, GRYDER_PAX3FOXO1_ENHANCERS_KO_DOWN, GOBP_INTRACELLULAR_TRANSPORT, DELACROIX_RAR_BOUND_ES, GOCC_FHF_COMPLEX

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

930 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHIP2A	HOOK3	Q86VS8	725
FHIP2A	HOOK1	Q9UJC3	723
FHIP2A	TRUB1	Q8WWH5	577
FHIP2A	FAM167B	Q9BTA0	560
FHIP2A	FHIP1A	Q05DH4	511
FHIP2A	FAM124A	Q86V42	485
FHIP2A	HOOK2	Q96ED9	485
FHIP2A	AKTIP	Q9H8T0	469
FHIP2A	TEX35	Q5T0J7	459
FHIP2A	ZNF704	Q6ZNC4	445
FHIP2A	C16orf90	A8MZG2	432
FHIP2A	FCF1	Q9Y324	419
FHIP2A	ZNF878	C9JN71	419
FHIP2A	FRMPD2	Q68DX3	411
FHIP2A	ATRNL1	Q5VV63	391

IntAct

32 interactions, top by confidence:

A	B	Type	Score
POC5	CETN3	psi-mi:“MI:0914”(association)	0.920
HOOK2	FHIP2A	psi-mi:“MI:0915”(physical association)	0.540
HOOK2	FHIP2A	psi-mi:“MI:0914”(association)	0.540
FAM9B	GEMIN2	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
PARP2	FHIP2A	psi-mi:“MI:0557”(adp ribosylation reaction)	0.440
FHIP2A	lon	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
TNFSF13B	HEATR1	psi-mi:“MI:0914”(association)	0.350
rep	B4GALT3	psi-mi:“MI:0914”(association)	0.350
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
EFNB1	KRBA1	psi-mi:“MI:0914”(association)	0.350
KLHL2	DCTN6	psi-mi:“MI:0914”(association)	0.350
WHAMMP3	EXOC5	psi-mi:“MI:0914”(association)	0.350
TNFSF13B	TNPO2	psi-mi:“MI:0914”(association)	0.350
CHP2	PCDH7	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
NPTXR	ACACB	psi-mi:“MI:0914”(association)	0.350
WHAMMP3	CCDC22	psi-mi:“MI:0914”(association)	0.350
FAM9B	CIBAR1	psi-mi:“MI:0914”(association)	0.350
GPR17	C1QTNF9B	psi-mi:“MI:0914”(association)	0.350
S1PR3	STXBP3	psi-mi:“MI:0914”(association)	0.350
SLC27A2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
SLC27A4	IPO5	psi-mi:“MI:0914”(association)	0.350
SLC35E1	IPO8	psi-mi:“MI:0914”(association)	0.350
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270
FHIP2B	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (76): FAM160B1 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Synthetic Lethality), FAM160B1 (Proximity Label-MS), FAM160B1 (Proximity Label-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Proximity Label-MS), FAM160B1 (Proximity Label-MS), FAM160B1 (Affinity Capture-MS), FAM160B1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNG7, A0JPF5, A0JPG1, A2VE70, B0V207, B1AY13, B4F766, F1QFR9, F1R2X6, O17482, O43156, P49021, P50851, Q05DH4, Q0P4Q0, Q15021, Q4S6U8, Q505K2, Q5PNP1, Q5RAW5, Q5SP90, Q5SSW2, Q5W0V3, Q5ZLW3, Q6DCP6, Q6IN85, Q6INN7, Q6NRP2, Q6P2K6, Q7RTS9, Q80TR8, Q80YR2, Q86V87, Q8CDM8, Q8CHY3, Q8IV36, Q8IY22, Q8K2Z4, Q8NFP9, Q8R1F6

Diamond homologs: A0JNG7, A0JPF5, A0JPG1, Q0P4Q0, Q5W0V3, Q80YR2, Q86V87, Q8CDM8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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 transport	7	8.5×	3e-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	1
Uncertain significance	59
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
633777	NM_020940.4(FHIP2A):c.115G>T (p.Glu39Ter)	Likely pathogenic

SpliceAI

2434 predictions. Top by Δscore:

Variant	Effect	Δscore
10:114822078:G:GT	donor_gain	1.0000
10:114822124:G:GG	donor_gain	1.0000
10:114822124:GTAAG:G	donor_loss	1.0000
10:114822125:T:A	donor_loss	1.0000
10:114830847:TGTA:T	acceptor_loss	1.0000
10:114830848:GTA:G	acceptor_loss	1.0000
10:114830850:A:AG	acceptor_gain	1.0000
10:114830850:AGCTT:A	acceptor_gain	1.0000
10:114830851:G:GT	acceptor_gain	1.0000
10:114830851:GC:G	acceptor_gain	1.0000
10:114830851:GCT:G	acceptor_gain	1.0000
10:114830851:GCTT:G	acceptor_gain	1.0000
10:114830851:GCTTG:G	acceptor_gain	1.0000
10:114830928:CAG:C	donor_loss	1.0000
10:114830929:AGGT:A	donor_loss	1.0000
10:114830930:GGTAA:G	donor_loss	1.0000
10:114830931:GTAAG:G	donor_loss	1.0000
10:114830932:T:G	donor_loss	1.0000
10:114833228:TTTA:T	acceptor_loss	1.0000
10:114833229:TTA:T	acceptor_loss	1.0000
10:114833231:A:AG	acceptor_gain	1.0000
10:114833231:AGAT:A	acceptor_gain	1.0000
10:114833232:G:GC	acceptor_gain	1.0000
10:114833232:GA:G	acceptor_gain	1.0000
10:114833232:GAT:G	acceptor_gain	1.0000
10:114833232:GATG:G	acceptor_gain	1.0000
10:114833232:GATGA:G	acceptor_gain	1.0000
10:114833400:GAT:G	donor_gain	1.0000
10:114833403:G:GG	donor_gain	1.0000
10:114836120:ACAG:A	acceptor_loss	1.0000

AlphaMissense

5001 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:114822113:C:A	A12D	1.000
10:114830894:T:A	W30R	1.000
10:114830894:T:C	W30R	1.000
10:114833275:T:C	L56P	1.000
10:114833296:T:C	L63P	1.000
10:114833342:T:G	C78W	1.000
10:114833356:T:C	L83P	1.000
10:114843933:T:A	W337R	1.000
10:114843933:T:C	W337R	1.000
10:114843935:G:C	W337C	1.000
10:114843935:G:T	W337C	1.000
10:114848652:T:C	L573P	1.000
10:114848714:T:C	Y594H	1.000
10:114848718:T:C	L595P	1.000
10:114848727:C:A	A598D	1.000
10:114861244:T:C	L701P	1.000
10:114861298:G:C	R719T	1.000
10:114861298:G:T	R719I	1.000
10:114861299:A:C	R719S	1.000
10:114861299:A:T	R719S	1.000
10:114861460:G:C	G740R	1.000
10:114861478:G:A	E746K	1.000
10:114861486:T:G	C748W	1.000
10:114861489:G:C	K749N	1.000
10:114861489:G:T	K749N	1.000
10:114861494:T:C	L751P	1.000
10:114861497:C:A	A752E	1.000
10:114861500:C:A	A753E	1.000
10:114822112:G:C	A12P	0.999
10:114830883:T:C	F26S	0.999

dbSNP variants (sampled 300 via entrez): RS1000006568 (10:114891732 T>A), RS1000021851 (10:114856491 G>A), RS1000039000 (10:114827069 A>C), RS1000058436 (10:114876808 A>G), RS1000106786 (10:114898302 G>A), RS1000179958 (10:114893267 T>A), RS1000191183 (10:114877745 A>C), RS1000223351 (10:114849794 C>T), RS1000232640 (10:114823323 A>G), RS1000248257 (10:114860581 A>C,G), RS1000258794 (10:114874747 G>A,C,T), RS1000271336 (10:114863448 A>G), RS1000273383 (10:114843094 T>A,G), RS1000283048 (10:114843392 G>A), RS1000291459 (10:114875091 G>A)

Disease associations

OMIM: gene MIM:617312 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): syndromic intellectual disability (MONDO:0000508)

Orphanet (1): Rare genetic syndromic intellectual disability (Orphanet:183763)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008103_142	Bipolar disorder	3.000000e-06
GCST90011900_45	Serum alkaline phosphatase levels	4.000000e-09
GCST90013406_226	Liver enzyme levels (alkaline phosphatase)	2.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
bisphenol A	decreases methylation, increases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
salinomycin	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Rotenone	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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