F8A3

Summary

F8A3 (coagulation factor VIII associated 3, HGNC:31850) is a protein-coding gene on chromosome Xq28, encoding 40-kDa huntingtin-associated protein (P23610). RAB5A effector molecule that is involved in vesicular trafficking of early endosomes.

This gene is part of a region that is repeated three times on chromosome X, once in intron 22 of the F8 gene and twice closer to the Xq telomere. This record represents the most telomeric copy. Although its function is unknown, the observation that this gene is conserved in the mouse implies it has some function. Unlike factor VIII, this gene is transcribed abundantly in a wide variety of cell types.

Source: NCBI Gene 474384 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001007524

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31850
Approved symbol	F8A3
Name	coagulation factor VIII associated 3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000277150
Ensembl biotype	protein_coding
Entrez	474384

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000622749

RefSeq mRNA: 1 — MANE Select: NM_001007524 NM_001007524

CCDS: CCDS35463

Canonical transcript exons

ENST00000622749 — 1 exons

Exon	Start	End
ENSE00003730157	155456914	155458620

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 84.46.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	84.46	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.54	gold quality
granulocyte	CL:0000094	80.96	gold quality
apex of heart	UBERON:0002098	79.71	gold quality
leukocyte	CL:0000738	78.21	gold quality
monocyte	CL:0000576	77.34	gold quality
mucosa of stomach	UBERON:0001199	76.21	gold quality
cortical plate	UBERON:0005343	74.97	gold quality
skeletal muscle tissue	UBERON:0001134	74.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.51	gold quality
superior frontal gyrus	UBERON:0002661	72.00	gold quality
fundus of stomach	UBERON:0001160	71.45	gold quality
urinary bladder	UBERON:0001255	71.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	71.04	gold quality
right lobe of liver	UBERON:0001114	70.97	gold quality
gall bladder	UBERON:0002110	70.93	gold quality
lower esophagus mucosa	UBERON:0035834	70.82	gold quality
primary visual cortex	UBERON:0002436	70.65	gold quality
endocervix	UBERON:0000458	70.64	gold quality
blood	UBERON:0000178	70.20	gold quality
bone marrow cell	CL:0002092	69.21	gold quality
liver	UBERON:0002107	69.13	gold quality
bone marrow	UBERON:0002371	68.72	gold quality
colonic epithelium	UBERON:0000397	68.66	gold quality
placenta	UBERON:0001987	67.95	gold quality
myometrium	UBERON:0001296	67.74	gold quality
muscle tissue	UBERON:0002385	67.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	67.15	gold quality
uterine cervix	UBERON:0000002	66.46	gold quality
muscle of leg	UBERON:0001383	66.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.33

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	f8a	ENSDARG00000025518
mus_musculus	F8a	ENSMUSG00000078317
rattus_norvegicus	F8a1	ENSRNOG00000080664
rattus_norvegicus		ENSRNOG00000085632
drosophila_melanogaster	Hap40	FBGN0030671

Paralogs (2): F8A2 (ENSG00000288709), F8A1 (ENSG00000288722)

Protein

Protein identifiers

40-kDa huntingtin-associated protein — P23610 (reviewed: P23610)

Alternative names: CpG island protein, Factor VIII intron 22 protein

All UniProt accessions (1): P23610

UniProt curated annotations — full annotation on UniProt →

Function. RAB5A effector molecule that is involved in vesicular trafficking of early endosomes. Mediates the recruitment of HTT by RAB5A onto early endosomes. The HTT-F8A1/F8A2/F8A3-RAB5A complex stimulates early endosomal interaction with actin filaments and inhibits interaction with microtubules, leading to the reduction of endosome motility.

Subunit / interactions. Interacts with HTT (via C-terminus). Interacts with RAB5A. Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A onto early endosomes.

Subcellular location. Cytoplasm. Nucleus. Early endosome. Nuclear body.

Tissue specificity. Produced abundantly in a wide variety of cell types.

Disease relevance. Up-regulated in brain tissue from patients affected by Huntington’s disease (at protein level). In a Huntington’s disease mouse model overexpression of F8A1/F8A2/F8A3 impairs proteasome activity leading to the accumulation of mutant HTT and causes defective mitochondrial functions.

RefSeq proteins (1): NP_001007525* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR039494	F8A	Family

UniProt features (27 total): helix 13, turn 3, strand 3, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1, short sequence motif 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9PMW	ELECTRON MICROSCOPY	2.1
9PN0	ELECTRON MICROSCOPY	2.3
9YR6	ELECTRON MICROSCOPY	2.3
6X9O	ELECTRON MICROSCOPY	2.6
8VLX	ELECTRON MICROSCOPY	2.6
8W15	ELECTRON MICROSCOPY	2.72
8SAH	ELECTRON MICROSCOPY	3.2
7DXJ	ELECTRON MICROSCOPY	3.6
6EZ8	ELECTRON MICROSCOPY	4
7DXK	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23610-F1	78.88	0.42

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_VESICLE_LOCALIZATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_VESICLE_CYTOSKELETAL_TRAFFICKING, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ORGANELLE_LOCALIZATION, GOBP_REGULATION_OF_PROTEOLYSIS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, GOCC_NUCLEAR_BODY, GOBP_PROTEOLYSIS

GO Biological Process (2): vesicle cytoskeletal trafficking (GO:0099518), negative regulation of proteasomal protein catabolic process (GO:1901799)

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

GO Cellular Component (5): nucleus (GO:0005634), early endosome (GO:0005769), nuclear body (GO:0016604), cytoplasm (GO:0005737), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton-dependent intracellular transport	1
establishment of vesicle localization	1
proteasomal protein catabolic process	1
negative regulation of protein catabolic process	1
regulation of proteasomal protein catabolic process	1
binding	1
intracellular membrane-bounded organelle	1
endosome	1
nucleoplasm	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F8A3	HTT	P42858	974
F8A3	RAB5A	P20339	953
F8A3	HAP1	P54257	583
F8A3	APPL1	Q9UKG1	481
F8A3	REPIN1	Q9BWE0	480
F8A3	NAPB	Q9H115	448
F8A3	ANKFY1	Q9P2R3	388
F8A3	RAB11A	P24410	365
F8A3	RAB8A	P24407	360
F8A3	KIF16B	Q96L93	349
F8A3	RBSN	Q9H1K0	348
F8A3	AP2S1	P53680	336
F8A3	NPIPB15	A6NHN6	327
F8A3	CLIC2	O15247	324
F8A3	SPRY3	O43610	323

IntAct

11 interactions, top by confidence:

A	B	Type	Score
F8A1	HTT	psi-mi:“MI:0915”(physical association)	0.780
RAB30	UBB	psi-mi:“MI:0914”(association)	0.530
F8A1	MTNR1A	psi-mi:“MI:0915”(physical association)	0.000
SH3GLB1	F8A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): F8A1 (Affinity Capture-MS), F8A1 (Two-hybrid), F8A1 (Two-hybrid), F8A1 (Affinity Capture-Western), KPTN (Affinity Capture-MS), RASA2 (Affinity Capture-MS), ITFG2 (Affinity Capture-MS), HTT (Affinity Capture-MS), HTT (Affinity Capture-MS), CLUH (Affinity Capture-MS), ITFG2 (Affinity Capture-MS), F8A1 (Affinity Capture-MS), KPTN (Affinity Capture-MS), F8A1 (Proximity Label-MS), F8A1 (Positive Genetic)

ESM2 similar proteins: A5A779, A6NLP5, A8E7I5, C5IJB0, F1MX48, I3L5V6, M0RDU0, O35465, O95801, P23610, P36915, P36916, P97452, Q00558, Q08602, Q0P5H9, Q14137, Q14318, Q17QX2, Q2TBQ9, Q2YD98, Q3B7U9, Q3SZV0, Q4R588, Q4R8D2, Q5EA80, Q5NVK5, Q5R8E2, Q5RA07, Q5TM59, Q66H45, Q68G30, Q6AY79, Q6IMX7, Q6P597, Q6P9Z4, Q6SZW1, Q7YR35, Q810A3, Q8C3I8

Diamond homologs: M0RDU0, P23610, Q00558

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

116 predictions. Top by Δscore:

Variant	Effect	Δscore
X:155457810:T:TA	donor_gain	0.5300
X:155457942:TG:T	donor_gain	0.4700
X:155457712:T:TA	donor_gain	0.4400
X:155458419:T:TA	donor_gain	0.4200
X:155457449:C:CC	acceptor_gain	0.4100
X:155458420:C:CA	donor_gain	0.3900
X:155457597:T:TA	donor_gain	0.3800
X:155457675:T:A	donor_gain	0.3500
X:155457489:ACTC:A	donor_gain	0.3400
X:155457490:CTCC:C	donor_gain	0.3400
X:155457444:CCGGC:C	acceptor_gain	0.3300
X:155457445:CGGCC:C	acceptor_gain	0.3300
X:155457571:TCTCC:T	donor_gain	0.3300
X:155458483:T:TA	donor_gain	0.3300
X:155457367:C:CA	donor_gain	0.3200
X:155457552:G:C	donor_gain	0.3200
X:155457603:T:TA	donor_gain	0.3200
X:155457632:C:CC	acceptor_gain	0.3200
X:155457709:A:AC	donor_gain	0.3200
X:155457710:C:CC	donor_gain	0.3200
X:155457792:TC:T	acceptor_gain	0.3200
X:155457304:AATT:A	donor_gain	0.3100
X:155457336:G:GT	acceptor_gain	0.3000
X:155457492:C:A	donor_gain	0.3000
X:155457631:A:AC	acceptor_gain	0.3000
X:155457964:C:CA	donor_gain	0.3000
X:155457307:T:A	donor_gain	0.2900
X:155457445:CGGC:C	acceptor_gain	0.2900
X:155458460:G:A	donor_gain	0.2900
X:155457569:CATCT:C	donor_gain	0.2800

AlphaMissense

2313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:155458483:T:C	K40E	0.999
X:155458490:G:C	F37L	0.999
X:155458490:G:T	F37L	0.999
X:155458491:A:G	F37S	0.999
X:155458492:A:G	F37L	0.999
X:155458525:A:C	Y26D	0.999
X:155458396:A:G	C69R	0.998
X:155458481:C:A	K40N	0.998
X:155458481:C:G	K40N	0.998
X:155458507:T:C	K32E	0.998
X:155457537:A:G	L355P	0.997
X:155457709:A:C	Y298D	0.997
X:155458375:A:G	C76R	0.997
X:155458401:G:T	A67D	0.997
X:155458431:A:G	L57P	0.997
X:155458451:G:C	F50L	0.997
X:155458451:G:T	F50L	0.997
X:155458452:A:C	F50C	0.997
X:155458452:A:G	F50S	0.997
X:155458453:A:G	F50L	0.997
X:155458479:G:T	P41Q	0.997
X:155458491:A:C	F37C	0.997
X:155458498:T:C	K35E	0.997
X:155458499:C:A	K34N	0.997
X:155458499:C:G	K34N	0.997
X:155458505:C:A	K32N	0.997
X:155458505:C:G	K32N	0.997
X:155458525:A:G	Y26H	0.997
X:155458525:A:T	Y26N	0.997
X:155457774:A:G	L276P	0.996

dbSNP variants (sampled 201 via entrez): RS1158091197 (X:155456565 CGGGG>C,CG,CGG,CGGG,CGGGGG,CGGGGGG), RS11630 (X:155457167 G>A), RS1172470193 (X:155459010 C>A,G), RS1172579190 (X:155456595 T>A), RS1173128502 (X:155458971 A>C,G), RS1175078700 (X:155459030 C>T), RS1185522752 (X:155456566 G>A), RS1192481441 (X:155458989 A>C,G), RS1195707256 (X:155456569 GGGGGAAA>G), RS1198938185 (X:155456679 C>T), RS12014338 (X:155456425 G>T), RS1207044841 (X:155458998 C>T), RS1209918810 (X:155456572 GGAA>G), RS1212636143 (X:155456751 A>G), RS1216690549 (X:155456845 T>C)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
abrine	decreases expression	1
Capecitabine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects response to substance	1
Copper	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Ozone	increases abundance, affects expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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