FHIP1A

Summary

FHIP1A (FHF complex subunit HOOK interacting protein 1A, HGNC:34237) is a protein-coding gene on chromosome 4q31.3, encoding FHF complex subunit HOOK-interacting protein 1A (Q05DH4). Probable component of the FTS/Hook/FHIP complex (FHF complex).

Involved in protein localization to perinuclear region of cytoplasm.

Source: NCBI Gene 729830 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 189 total
• MANE Select transcript: NM_001109977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34237
Approved symbol	FHIP1A
Name	FHF complex subunit HOOK interacting protein 1A
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43373, FHIP-L
Ensembl gene	ENSG00000164142
Ensembl biotype	protein_coding
Entrez	729830

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000435205, ENST00000503146, ENST00000505231, ENST00000508198, ENST00000508664, ENST00000511501, ENST00000512597, ENST00000513086, ENST00000513962, ENST00000883036, ENST00000883037, ENST00000883038, ENST00000883039, ENST00000883040, ENST00000923453, ENST00000923454

RefSeq mRNA: 2 — MANE Select: NM_001109977 NM_001109977, NM_001348694

CCDS: CCDS47146

Canonical transcript exons

ENST00000435205 — 14 exons

Exon	Start	End
ENSE00001403367	151454701	151454808
ENSE00001409305	151482524	151482648
ENSE00003756037	151662501	151670503
ENSE00003843304	151409176	151409465
ENSE00003889911	151638677	151638756
ENSE00003891067	151649459	151650592
ENSE00003891100	151577450	151578076
ENSE00003891398	151588840	151588926
ENSE00003892600	151646558	151646748
ENSE00003892703	151656232	151656410
ENSE00003892881	151566138	151566364
ENSE00003893316	151629702	151629869
ENSE00003894138	151586641	151586799
ENSE00003895936	151656760	151656898

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 96.47.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1179 / max 280.2040, expressed in 879 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50011	3.8496	802
50012	0.5211	292
50013	0.4485	213
50010	0.1196	49
50014	0.0947	31
50015	0.0843	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.82	gold quality
quadriceps femoris	UBERON:0001377	90.23	gold quality
tibialis anterior	UBERON:0001385	90.16	gold quality
vastus lateralis	UBERON:0001379	89.82	gold quality
skeletal muscle tissue	UBERON:0001134	89.70	gold quality
deltoid	UBERON:0001476	89.65	gold quality
upper arm skin	UBERON:0004263	89.51	gold quality
cartilage tissue	UBERON:0002418	89.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.02	gold quality
oviduct epithelium	UBERON:0004804	87.15	gold quality
gingival epithelium	UBERON:0001949	87.07	gold quality
gastrocnemius	UBERON:0001388	86.84	gold quality
muscle of leg	UBERON:0001383	86.76	gold quality
pancreatic ductal cell	CL:0002079	86.69	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.16	gold quality
muscle tissue	UBERON:0002385	85.75	gold quality
lower esophagus mucosa	UBERON:0035834	85.55	gold quality
gingiva	UBERON:0001828	84.96	gold quality
biceps brachii	UBERON:0001507	84.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.87	gold quality
esophagus squamous epithelium	UBERON:0006920	83.80	gold quality
oocyte	CL:0000023	83.51	gold quality
amniotic fluid	UBERON:0000173	81.69	gold quality
ileal mucosa	UBERON:0000331	81.68	gold quality
skin of abdomen	UBERON:0001416	80.39	gold quality
zone of skin	UBERON:0000014	80.36	gold quality
skin of leg	UBERON:0001511	80.26	gold quality
secondary oocyte	CL:0000655	79.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.42	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.86
E-ENAD-17	no	130.32
E-MTAB-6142	no	35.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting FHIP1A, 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-4262	100.00	73.26	3931
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
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-4534	99.99	66.58	1907
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482

Literature-anchored findings (GeneRIF, showing 1)

• this report implicates a novel recessive germline mutation in FAM160A1 with familial NKTL. (PMID:30420729)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fhip1aa	ENSDARG00000061021
danio_rerio	fhip1ab	ENSDARG00000102585
mus_musculus	Fhip1a	ENSMUSG00000051000
rattus_norvegicus	Fhip1a	ENSRNOG00000048256
drosophila_melanogaster	CG3558	FBGN0025681
caenorhabditis_elegans		WBGENE00015485

Paralogs (3): FHIP1B (ENSG00000051009), FHIP2A (ENSG00000151553), FHIP2B (ENSG00000158863)

Protein

Protein identifiers

FHF complex subunit HOOK-interacting protein 1A — Q05DH4 (reviewed: Q05DH4)

Alternative names: FTS- and Hook-interacting protein like

All UniProt accessions (5): D6RAG2, D6RBF5, D6RDL4, D6RF38, Q05DH4

UniProt curated annotations — full annotation on UniProt →

Function. Probable component of the FTS/Hook/FHIP complex (FHF complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell.

Subunit / interactions. May be a component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3. May interact directly with AKTIP/FTS.

Similarity. Belongs to the FHIP family.

RefSeq proteins (2): NP_001103447, NP_001335623 (=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 (9 total): compositionally biased region 4, region of interest 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05DH4-F1	65.15	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, WATANABE_ULCERATIVE_COLITIS_WITH_CANCER_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GAVIN_FOXP3_TARGETS_CLUSTER_P3, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_DN, GOBP_INTRACELLULAR_TRANSPORT, GOCC_FHF_COMPLEX, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GSE13522_CTRL_VS_T_CRUZI_G_STRAIN_INF_SKIN_DN, GOBP_MICROTUBULE_BASED_TRANSPORT, GSE14699_NAIVE_VS_ACT_CD8_TCELL_UP, UBN1_TARGET_GENES, ZNF423_TARGET_GENES, ZNF561_TARGET_GENES

GO Biological Process (1): protein localization to perinuclear region of cytoplasm (GO:1905719)

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
intracellular protein localization	1
binding	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FHIP1A	AKTIP	Q9H8T0	606
FHIP1A	LZTS2	Q9BRK4	596
FHIP1A	HOOK3	Q86VS8	539
FHIP1A	FHIP2A	Q5W0V3	511
FHIP1A	SIPA1L1	O43166	508
FHIP1A	GULP1	Q9UBP9	499
FHIP1A	GPR26	Q8NDV2	497
FHIP1A	HOOK1	Q9UJC3	477
FHIP1A	BRINP1	O60477	457
FHIP1A	HOOK2	Q96ED9	443
FHIP1A	WDR35	Q9P2L0	441
FHIP1A	LRIG3	Q6UXM1	436
FHIP1A	MYO6	Q9UM54	435
FHIP1A	URI1	O94763	432
FHIP1A	ATG9A	Q7Z3C6	405
FHIP1A	SPATA31F1	Q6ZU69	405

IntAct

17 interactions, top by confidence:

A	B	Type	Score
HOOK3	FHIP1A	psi-mi:“MI:0914”(association)	0.710
FHIP1A	AKTIP	psi-mi:“MI:0915”(physical association)	0.640
AKTIP	FHIP1A	psi-mi:“MI:0915”(physical association)	0.640
FHIP1A	FHIP1A	psi-mi:“MI:0915”(physical association)	0.520
AP4M1	FHIP1A	psi-mi:“MI:0915”(physical association)	0.520
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
AKTIP	FHIP1A	psi-mi:“MI:0914”(association)	0.350
FHIP1A	HOOK2	psi-mi:“MI:0914”(association)	0.350
AKTIP	PGGT1B	psi-mi:“MI:0914”(association)	0.350
AKTIP	ALDH1A2	psi-mi:“MI:0914”(association)	0.350
HOOK3	ETHE1	psi-mi:“MI:0914”(association)	0.350
FHIP1A	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
MYO6	GIPC1	psi-mi:“MI:2364”(proximity)	0.270
GIPC1	STRN	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (43): FAM160A1 (Affinity Capture-MS), FAM160A1 (Affinity Capture-MS), FAM160A1 (Affinity Capture-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Affinity Capture-RNA), FAM160A1 (Proximity Label-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Affinity Capture-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Proximity Label-MS), FAM160A1 (Proximity Label-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: A7S6A1, A7YY62, B0X755, B3MLI0, B3NAN9, B4G8N3, B4JQY3, B4KJS5, B4LQW4, B4MTY2, B4NXB9, B5DI68, Q05DH4, Q17AI4, Q3U2I3, Q505K2, Q5R8V2, Q66H54, Q7PZ36, Q8N612, Q9VQK0, A8XW52, B0V207, Q11187, A8P7J8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	168
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3539 predictions. Top by Δscore:

Variant	Effect	Δscore
4:151409464:AGGTA:A	donor_loss	1.0000
4:151415712:T:A	acceptor_gain	1.0000
4:151578072:GTCCA:G	donor_gain	1.0000
4:151578073:TCCA:T	donor_gain	1.0000
4:151578073:TCCAG:T	donor_loss	1.0000
4:151578076:AG:A	donor_loss	1.0000
4:151578077:G:GG	donor_gain	1.0000
4:151578078:TAAG:T	donor_loss	1.0000
4:151586863:GAT:G	donor_gain	1.0000
4:151629694:T:TA	acceptor_gain	1.0000
4:151629696:TCCTA:T	acceptor_loss	1.0000
4:151629697:CCTA:C	acceptor_loss	1.0000
4:151629698:CTA:C	acceptor_loss	1.0000
4:151629699:TA:T	acceptor_loss	1.0000
4:151629700:A:AG	acceptor_gain	1.0000
4:151629700:AGGT:A	acceptor_gain	1.0000
4:151629701:G:GG	acceptor_gain	1.0000
4:151629701:GGT:G	acceptor_gain	1.0000
4:151629701:GGTG:G	acceptor_gain	1.0000
4:151629865:TTCGG:T	donor_loss	1.0000
4:151629866:TCGGG:T	donor_loss	1.0000
4:151629867:CGGG:C	donor_loss	1.0000
4:151629868:GG:G	donor_gain	1.0000
4:151629868:GGGTA:G	donor_loss	1.0000
4:151629869:GG:G	donor_gain	1.0000
4:151629869:GGTA:G	donor_loss	1.0000
4:151629870:G:GC	donor_loss	1.0000
4:151629870:G:GG	donor_gain	1.0000
4:151629871:T:G	donor_loss	1.0000
4:151646708:G:GT	donor_gain	1.0000

AlphaMissense

6874 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:151588889:G:A	G314E	1.000
4:151588891:T:C	F315L	1.000
4:151588892:T:C	F315S	1.000
4:151588893:T:A	F315L	1.000
4:151588893:T:G	F315L	1.000
4:151588904:T:A	V319D	1.000
4:151629739:T:C	L339P	1.000
4:151629841:T:C	L373P	1.000
4:151577654:T:A	W104R	0.999
4:151577654:T:C	W104R	0.999
4:151577946:T:C	L201P	0.999
4:151577988:C:A	A215D	0.999
4:151577991:G:C	R216P	0.999
4:151578071:T:C	C243R	0.999
4:151586645:T:A	L246H	0.999
4:151586645:T:C	L246P	0.999
4:151586653:G:A	G249R	0.999
4:151586653:G:C	G249R	0.999
4:151586653:G:T	G249W	0.999
4:151586654:G:A	G249E	0.999
4:151586657:T:A	L250H	0.999
4:151586657:T:C	L250P	0.999
4:151586659:A:C	S251R	0.999
4:151586661:T:A	S251R	0.999
4:151586661:T:G	S251R	0.999
4:151586663:G:A	G252D	0.999
4:151586666:T:C	L253P	0.999
4:151586668:T:G	Y254D	0.999
4:151586678:T:C	L257P	0.999
4:151586774:T:C	L289P	0.999

dbSNP variants (sampled 300 via entrez): RS1000011589 (4:151474321 A>G), RS10000281 (4:151599338 C>G), RS1000039283 (4:151541486 A>G), RS1000040417 (4:151500276 G>C), RS1000064233 (4:151427882 A>G,T), RS1000074548 (4:151522750 A>C), RS1000075014 (4:151658466 G>A), RS1000089876 (4:151448932 A>G), RS1000090944 (4:151568144 A>G,T), RS1000117731 (4:151513451 T>A), RS1000125462 (4:151632721 A>G), RS1000130561 (4:151543675 T>C), RS1000143946 (4:151459469 A>G), RS1000147660 (4:151523044 C>A), RS1000155853 (4:151500826 G>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004603_224	Platelet count	2.000000e-12
GCST004607_229	Plateletcrit	4.000000e-10
GCST010837_3	Intracerebral hemorrhage	6.000000e-06
GCST90000025_291	Appendicular lean mass	2.000000e-22
GCST90002400_673	Plateletcrit	1.000000e-26
GCST90002402_753	Platelet count	3.000000e-27
GCST90002407_449	White blood cell count	4.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases abundance, increases expression	2
Oxygen	decreases reaction, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression	1
fluorene-9-bisphenol	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
chromium hexavalent ion	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Nickel	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1

Clinical trials (associated diseases)

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