FHIP2B

Summary

FHIP2B (FHF complex subunit HOOK interacting protein 2B, HGNC:16492) is a protein-coding gene on chromosome 8p21.3, encoding FHF complex subunit HOOK-interacting protein 2B (Q86V87). Able to activate MAPK/ERK and TGFB signaling pathways.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 179 total
• MANE Select transcript: NM_022749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16492
Approved symbol	FHIP2B
Name	FHF complex subunit HOOK interacting protein 2B
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21801
Ensembl gene	ENSG00000158863
Ensembl biotype	protein_coding
OMIM	620230
Entrez	64760

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 retained_intron, 8 protein_coding, 2 nonsense_mediated_decay

ENST00000289921, ENST00000427751, ENST00000450006, ENST00000462914, ENST00000464226, ENST00000474579, ENST00000477614, ENST00000488968, ENST00000491733, ENST00000496599, ENST00000498344, ENST00000523633, ENST00000857905, ENST00000857906, ENST00000857907, ENST00000926214, ENST00000926215, ENST00000948578, ENST00000948579

RefSeq mRNA: 3 — MANE Select: NM_022749 NM_001354250, NM_001354251, NM_022749

CCDS: CCDS6021

Canonical transcript exons

ENST00000289921 — 17 exons

Exon	Start	End
ENSE00001041611	22101440	22101530
ENSE00001041666	22101708	22101851
ENSE00001041782	22099704	22099893
ENSE00001158958	22102175	22102315
ENSE00001243943	22100844	22100972
ENSE00001333750	22099284	22099360
ENSE00001333752	22098948	22099056
ENSE00001847683	22102793	22104911
ENSE00003483073	22102528	22102628
ENSE00003513197	22094440	22094518
ENSE00003524912	22098068	22098310
ENSE00003546900	22097717	22097839
ENSE00003556609	22097516	22097620
ENSE00003558746	22096337	22096509
ENSE00003640791	22098423	22098619
ENSE00003646356	22100594	22100739
ENSE00003843652	22089150	22089298

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 98.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.1946 / max 107.1437, expressed in 1803 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87709	8.7062	1778
87708	6.8222	1755
87710	1.6662	1035

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	98.02	gold quality
adenohypophysis	UBERON:0002196	97.85	gold quality
left lobe of thyroid gland	UBERON:0001120	97.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.49	gold quality
endocervix	UBERON:0000458	97.35	gold quality
ectocervix	UBERON:0012249	97.17	gold quality
apex of heart	UBERON:0002098	97.16	gold quality
lower esophagus mucosa	UBERON:0035834	97.14	gold quality
cerebellar hemisphere	UBERON:0002245	97.05	gold quality
body of uterus	UBERON:0009853	97.05	gold quality
minor salivary gland	UBERON:0001830	96.94	gold quality
cerebellar cortex	UBERON:0002129	96.88	gold quality
right uterine tube	UBERON:0001302	96.86	gold quality
left uterine tube	UBERON:0001303	96.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.73	gold quality
ascending aorta	UBERON:0001496	96.72	gold quality
lower esophagus	UBERON:0013473	96.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.71	gold quality
thoracic aorta	UBERON:0001515	96.66	gold quality
right ovary	UBERON:0002118	96.61	gold quality
skin of abdomen	UBERON:0001416	96.59	gold quality
metanephros cortex	UBERON:0010533	96.53	gold quality
pituitary gland	UBERON:0000007	96.51	gold quality
thyroid gland	UBERON:0002046	96.49	gold quality
body of stomach	UBERON:0001161	96.48	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.44	gold quality
tibial nerve	UBERON:0001323	96.40	gold quality
left ovary	UBERON:0002119	96.39	gold quality
body of pancreas	UBERON:0001150	96.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• Retinoic acid induced 16 enhances tumorigenesis and serves as a novel tumor marker for hepatocellular carcinoma. (PMID:22971576)
• RAI16 interacted with the type II regulatory subunit of protein kinase A(PKA-RIIalpha), acting as a novel protein kinase A anchoring protein (AKAP). In addition, RAI16 also interacted with heat shock protein 70 (HSP70) and 14-3-3theta;. (PMID:25900241)
• FAM160B1 deficit associated with microcephaly, severe intellectual disability, ataxia, behavioral abnormalities and speech problems. (PMID:31353455)
• Retinoid acid induced 16 deficiency aggravates colitis and colitis-associated tumorigenesis in mice. (PMID:31862898)
• Identification of retinoid acid induced 16 as a novel androgen receptor target in prostate cancer cells. (PMID:32014455)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhip2b	ENSDARG00000060029
mus_musculus	Fhip2b	ENSMUSG00000022095
rattus_norvegicus	Fhip2b	ENSRNOG00000012014
drosophila_melanogaster	CG3558	FBGN0025681
caenorhabditis_elegans		WBGENE00015485

Paralogs (3): FHIP1B (ENSG00000051009), FHIP2A (ENSG00000151553), FHIP1A (ENSG00000164142)

Protein

Protein identifiers

FHF complex subunit HOOK-interacting protein 2B — Q86V87 (reviewed: Q86V87)

Alternative names: Retinoic acid-induced protein 16

All UniProt accessions (2): Q86V87, F2Z2X3

UniProt curated annotations — full annotation on UniProt →

Function. Able to activate MAPK/ERK and TGFB signaling pathways. May regulate the activity of genes involved in intestinal barrier function and immunoprotective inflammation. May play a role in cell proliferation.

Tissue specificity. Expressed in liver.

Similarity. Belongs to the FHIP family.

RefSeq proteins (3): NP_001341179, NP_001341180, NP_073586* (*=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 (7 total): sequence variant 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86V87-F1	80.32	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GCAAGGA_MIR502, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, chr8p21, CCAGGGG_MIR331, GSE5503_MLN_DC_VS_PLN_DC_ACTIVATED_ALLOGENIC_TCELL_DN, SKIL_TARGET_GENES, ZNF184_TARGET_GENES, ZNF2_TARGET_GENES, MIR450B_5P, MIR137_3P, MIR661, MIR9986, MIR31_5P, GSE11924_TFH_VS_TH2_CD4_TCELL_UP, MIR3116

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHIP2B	HOOK3	Q86VS8	577
FHIP2B	HOOK1	Q9UJC3	538
FHIP2B	HOOK2	Q96ED9	514
FHIP2B	ANKFY1	Q9P2R3	471
FHIP2B	STMN4	Q9H169	459
FHIP2B	C9orf43	Q8TAL5	448
FHIP2B	AKTIP	Q9H8T0	440
FHIP2B	TMEM132A	Q24JP5	437
FHIP2B	PRKACG	P22612	424
FHIP2B	PRKACA	P17612	423
FHIP2B	PRKACB	P22694	421
FHIP2B	FHIP1B	Q8N612	403
FHIP2B	EFHB	Q8N7U6	400
FHIP2B	VPS16	Q9H269	395
FHIP2B	BPIFC	Q8NFQ6	385

IntAct

11 interactions, top by confidence:

A	B	Type	Score
HOOK2	FHIP2A	psi-mi:“MI:0914”(association)	0.540
FHIP2B	HOOK2	psi-mi:“MI:0914”(association)	0.420
HOOK1	FHIP2B	psi-mi:“MI:0914”(association)	0.420
HOOK3	FHIP2B	psi-mi:“MI:0914”(association)	0.420
FHIP2B	ZNF318	psi-mi:“MI:0915”(physical association)	0.400
FHIP2B	ZNF318	psi-mi:“MI:0914”(association)	0.350
SLC27A4	IPO5	psi-mi:“MI:0914”(association)	0.350
FHIP2B	VWA8	psi-mi:“MI:2364”(proximity)	0.270
HOOK2	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
	FHIP2B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): DYNC2H1 (Affinity Capture-MS), RECQL4 (Affinity Capture-MS), ZNF318 (Affinity Capture-MS), SMG8 (Affinity Capture-MS), FAM160B2 (Biochemical Activity), ZNF318 (Affinity Capture-MS), MYO5A (Affinity Capture-MS), FAM160B2 (Proximity Label-MS), FAM160B2 (Proximity Label-MS), FAM160B2 (Proximity Label-MS), ZNF318 (Affinity Capture-MS), TBC1D23 (Proximity Label-MS), FAM91A1 (Proximity Label-MS), GOLGA4 (Proximity Label-MS), GOLGA5 (Proximity Label-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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	141
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3265 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22089284:G:GT	donor_gain	1.0000
8:22089330:G:GT	donor_gain	1.0000
8:22094436:GCA:G	acceptor_loss	1.0000
8:22094437:CAG:C	acceptor_loss	1.0000
8:22094438:A:AG	acceptor_gain	1.0000
8:22094438:A:AT	acceptor_loss	1.0000
8:22094439:G:A	acceptor_loss	1.0000
8:22094439:G:GA	acceptor_gain	1.0000
8:22094439:GC:G	acceptor_gain	1.0000
8:22094439:GCGC:G	acceptor_gain	1.0000
8:22096325:A:AG	acceptor_gain	1.0000
8:22096326:A:G	acceptor_gain	1.0000
8:22096329:A:AG	acceptor_gain	1.0000
8:22096330:T:G	acceptor_gain	1.0000
8:22096333:TTAG:T	acceptor_loss	1.0000
8:22096335:A:AC	acceptor_loss	1.0000
8:22096335:A:AG	acceptor_gain	1.0000
8:22096335:AGAT:A	acceptor_gain	1.0000
8:22096336:G:GT	acceptor_gain	1.0000
8:22096336:GAT:G	acceptor_gain	1.0000
8:22096336:GATG:G	acceptor_gain	1.0000
8:22097507:T:TA	acceptor_gain	1.0000
8:22097514:A:AG	acceptor_gain	1.0000
8:22097515:G:GG	acceptor_gain	1.0000
8:22097703:T:TA	acceptor_gain	1.0000
8:22097704:G:A	acceptor_gain	1.0000
8:22097706:T:TA	acceptor_gain	1.0000
8:22097713:CCA:C	acceptor_loss	1.0000
8:22097715:A:AG	acceptor_gain	1.0000
8:22097716:G:GT	acceptor_gain	1.0000

AlphaMissense

4829 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22102852:T:C	L718P	0.998
8:22096379:T:C	L56P	0.997
8:22102292:A:C	S657R	0.997
8:22102294:C:A	S657R	0.997
8:22102294:C:G	S657R	0.997
8:22102847:G:C	K716N	0.997
8:22102847:G:T	K716N	0.997
8:22102858:C:A	A720D	0.997
8:22094482:T:A	W30R	0.996
8:22094482:T:C	W30R	0.996
8:22096400:T:C	L63P	0.996
8:22096460:T:C	L83P	0.996
8:22097520:C:A	P101H	0.996
8:22101454:T:A	V544D	0.996
8:22101511:T:A	V563D	0.996
8:22102855:C:A	A719D	0.996
8:22102857:G:C	A720P	0.996
8:22096388:T:G	M59R	0.995
8:22096449:C:G	C79W	0.995
8:22097604:T:A	V129D	0.995
8:22101442:T:C	F540S	0.995
8:22094484:G:C	W30C	0.994
8:22094484:G:T	W30C	0.994
8:22097519:C:T	P101S	0.994
8:22100966:T:A	V537D	0.994
8:22101441:T:C	F540L	0.994
8:22101443:C:A	F540L	0.994
8:22101443:C:G	F540L	0.994
8:22102298:T:C	F659L	0.994
8:22102300:C:A	F659L	0.994

dbSNP variants (sampled 300 via entrez): RS1000278986 (8:22093598 A>G), RS1000409059 (8:22098300 G>T), RS1000814521 (8:22088499 C>T), RS1000886131 (8:22093500 G>A), RS1000935564 (8:22087160 T>C), RS1000938080 (8:22093688 G>C), RS1000980278 (8:22103126 A>G), RS1001018445 (8:22094768 T>C), RS1001102400 (8:22089884 C>G,T), RS1001176187 (8:22098864 G>C), RS1001229993 (8:22099020 T>C,G), RS1001265276 (8:22087947 C>A), RS1001271035 (8:22097677 C>T), RS1001493551 (8:22092944 A>G,T), RS1001948777 (8:22090399 C>T)

Disease associations

OMIM: gene MIM:620230 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010303_56	Nevus count or cutaneous melanoma	2.000000e-09
GCST010304_54	Cutaneous malignant melanoma	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004632	nevus count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	3
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects cotreatment, decreases expression	2
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases 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
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Gold Compounds	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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