FAM76B

Summary

FAM76B (family with sequence similarity 76 member B, HGNC:28492) is a protein-coding gene on chromosome 11q21, encoding Protein FAM76B (Q5HYJ3). Negatively regulates the NF-kappa-B-mediated inflammatory pathway by preventing the translocation of HNRNPA2B1 from the nucleus to the cytoplasm.

Predicted to enable RNA binding activity. Involved in several processes, including mRNA stabilization; negative regulation of macrophage activation; and negative regulation of protein export from nucleus. Located in nuclear speck.

Source: NCBI Gene 143684 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_144664

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28492
Approved symbol	FAM76B
Name	family with sequence similarity 76 member B
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	MGC33371
Ensembl gene	ENSG00000077458
Ensembl biotype	protein_coding
Entrez	143684

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 5 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000358780, ENST00000398187, ENST00000535919, ENST00000536839, ENST00000537749, ENST00000538047, ENST00000538316, ENST00000540054, ENST00000541418, ENST00000542135, ENST00000543641, ENST00000545654, ENST00000545813

RefSeq mRNA: 2 — MANE Select: NM_144664 NM_001330357, NM_144664

CCDS: CCDS41700, CCDS81619

Canonical transcript exons

ENST00000358780 — 10 exons

Exon	Start	End
ENSE00001746136	95768953	95771650
ENSE00002290266	95789392	95789782
ENSE00003522165	95779879	95779926
ENSE00003544496	95775922	95776023
ENSE00003553232	95783065	95783264
ENSE00003583004	95779607	95779687
ENSE00003595225	95788499	95788563
ENSE00003644163	95778822	95778957
ENSE00003672470	95787624	95787678
ENSE00003680003	95786119	95786274

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2463 / max 104.1237, expressed in 1734 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121873	6.3954	1653
121874	2.4933	955
121872	1.3575	772

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.57	gold quality
calcaneal tendon	UBERON:0003701	96.18	gold quality
left testis	UBERON:0004533	95.10	gold quality
right testis	UBERON:0004534	94.62	gold quality
testis	UBERON:0000473	93.91	gold quality
epithelial cell of pancreas	CL:0000083	93.47	gold quality
sural nerve	UBERON:0015488	93.35	gold quality
tibial nerve	UBERON:0001323	92.95	gold quality
vermiform appendix	UBERON:0001154	92.67	gold quality
right lung	UBERON:0002167	92.55	gold quality
monocyte	CL:0000576	92.22	gold quality
left ovary	UBERON:0002119	91.80	gold quality
cortical plate	UBERON:0005343	91.59	gold quality
leukocyte	CL:0000738	91.53	gold quality
body of uterus	UBERON:0009853	91.36	gold quality
rectum	UBERON:0001052	91.22	gold quality
left lobe of thyroid gland	UBERON:0001120	91.21	gold quality
right ovary	UBERON:0002118	91.13	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.09	gold quality
lymph node	UBERON:0000029	91.03	gold quality
minor salivary gland	UBERON:0001830	91.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.01	gold quality
body of pancreas	UBERON:0001150	90.94	gold quality
right lobe of liver	UBERON:0001114	90.72	gold quality
mucosa of stomach	UBERON:0001199	90.58	gold quality
ganglionic eminence	UBERON:0004023	90.57	gold quality
thyroid gland	UBERON:0002046	90.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.43	gold quality
ovary	UBERON:0000992	90.37	gold quality
adrenal tissue	UBERON:0018303	90.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

203 targeting FAM76B, 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-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 2)

• FAM76B regulates NF-kappaB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1. (PMID:37643469)
• FAM76B regulates PI3K/Akt/NF-kappaB-mediated M1 macrophage polarization by influencing the stability of PIK3CD mRNA. (PMID:38421448)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam76b	ENSDARG00000012432
mus_musculus	Fam76b	ENSMUSG00000037808
rattus_norvegicus	Fam76b	ENSRNOG00000024863
drosophila_melanogaster	CG4452	FBGN0035981
caenorhabditis_elegans	K04F10.7	WBGENE00019399

Paralogs (2): FAM76A (ENSG00000009780), SENP8 (ENSG00000166192)

Protein

Protein identifiers

Protein FAM76B — Q5HYJ3 (reviewed: Q5HYJ3)

All UniProt accessions (5): Q5HYJ3, F5GX09, F5H215, F5H5F4, F5H6T9

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates the NF-kappa-B-mediated inflammatory pathway by preventing the translocation of HNRNPA2B1 from the nucleus to the cytoplasm. Inhibits the PI3K/Akt/NF-kappa-B pathway-mediated polarization of M1 macrophages by binding to and stabilizing PIK3CD mRNA, resulting in increased levels of PIK3CD protein and increased levels of phosphorylated downstream target AKT which leads to decreased NF-kappa-B signaling.

Subunit / interactions. Interacts with HNRNPA2B1 (via C-terminus); the interaction results in retention of HNRNPA2B1 in the nucleus and inhibition of the NF-kappa-B-mediated inflammatory pathway.

Subcellular location. Nucleus speckle.

Domain organisation. The basic polyhistidine region acts as a targeting signal to nuclear speckles.

Similarity. Belongs to the FAM76 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5HYJ3-1	1	yes
Q5HYJ3-2	2
Q5HYJ3-3	3

RefSeq proteins (2): NP_001317286, NP_653265* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032017	FAM76	Family

Pfam: PF16046

UniProt features (20 total): modified residue 5, sequence conflict 4, compositionally biased region 4, splice variant 3, initiator methionine 1, chain 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5HYJ3-F1	76.41	0.52

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 (5): 148, 193, 215, 2, 22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 253 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_REGULATION_OF_PROTEIN_EXPORT_FROM_NUCLEUS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NUCLEAR_TRANSPORT, GTGCCTT_MIR506, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, YGACNNYACAR_UNKNOWN, CAGCAGG_MIR370, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (4): negative regulation of macrophage activation (GO:0043031), negative regulation of protein export from nucleus (GO:0046826), mRNA stabilization (GO:0048255), negative regulation of inflammatory response (GO:0050728)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nuclear speck (GO:0016607), nucleus (GO:0005634), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of leukocyte activation	1
macrophage activation	1
regulation of macrophage activation	1
protein export from nucleus	1
negative regulation of nucleocytoplasmic transport	1
regulation of protein export from nucleus	1
maintenance of protein location in nucleus	1
negative regulation of intracellular protein transport	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
nucleic acid binding	1
binding	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM76B	ARL2BP	Q9Y2Y0	533
FAM76B	DYRK1B	Q9Y463	422
FAM76B	CEP57	Q86XR8	400
FAM76B	RSRC2	Q7L4I2	400
FAM76B	ZBTB45	Q96K62	399
FAM76B	PPP1R8	Q12972	366
FAM76B	ZNF227	Q86WZ6	354
FAM76B	DYRK1A	Q13627	353
FAM76B	GOLGA1	Q92805	343
FAM76B	TTC23	Q5W5X9	339
FAM76B	SCRN3	Q0VDG4	336
FAM76B	CCDC82	Q8N4S0	333
FAM76B	FAM216A	Q8WUB2	330
FAM76B	MITD1	Q8WV92	322
FAM76B	PCDHGA5	Q9Y5G8	311

IntAct

59 interactions, top by confidence:

A	B	Type	Score
FAM76B	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.560
FAM76B	KRTAP10-11	psi-mi:“MI:0915”(physical association)	0.560
FAM76B		psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	FAM76B	psi-mi:“MI:0915”(physical association)	0.560
FAM76B	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	FAM76B	psi-mi:“MI:0915”(physical association)	0.560
FAM76B	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
FAM76B	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
FAM76B	KRTAP4-7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-5	FAM76B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	FAM76B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	FAM76B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-7	FAM76B	psi-mi:“MI:0915”(physical association)	0.560
FAM76B	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.560
FAM76B	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-11	FAM76B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (127): FAM76B (Two-hybrid), FAM76B (Two-hybrid), FAM76B (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-11 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), FAM76B (Affinity Capture-MS), SORL1 (Affinity Capture-MS), ADO (Affinity Capture-MS), FAM76B (Affinity Capture-MS), FAM76B (Two-hybrid)

ESM2 similar proteins: A4FVD8, A5D7H2, O14795, O43237, O55047, O70585, O75446, O88574, P58405, P84060, Q02241, Q0VA03, Q13033, Q14161, Q28H91, Q2TAD4, Q4KUS2, Q4R5P6, Q5EA89, Q5HYJ3, Q5R7U7, Q5RE09, Q5SQF8, Q5ZJ65, Q62768, Q6NYV5, Q6PBM7, Q6PDL0, Q80XP8, Q80YA9, Q811S7, Q86UE8, Q8BIK4, Q8C0V0, Q8CBY8, Q8TAV0, Q8WXI2, Q90ZY6, Q922G2, Q96EZ8

Diamond homologs: Q566M1, Q5EA89, Q5HYJ3, Q5ZJ65, Q6DEE7, Q6PBM7, Q80XP8, Q8TAV0, Q922G2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	8	15.4×	5e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1435 predictions. Top by Δscore:

Variant	Effect	Δscore
11:95775917:GTTAC:G	donor_loss	1.0000
11:95775918:TTACC:T	donor_loss	1.0000
11:95775919:TA:T	donor_loss	1.0000
11:95775920:A:T	donor_loss	1.0000
11:95775921:C:CA	donor_loss	1.0000
11:95776019:GTTAA:G	acceptor_gain	1.0000
11:95776020:TTAA:T	acceptor_gain	1.0000
11:95776021:TAA:T	acceptor_gain	1.0000
11:95776022:AA:A	acceptor_gain	1.0000
11:95776022:AAC:A	acceptor_loss	1.0000
11:95776024:C:CC	acceptor_gain	1.0000
11:95776024:CTG:C	acceptor_loss	1.0000
11:95776025:T:G	acceptor_loss	1.0000
11:95776032:T:TC	acceptor_gain	1.0000
11:95778816:TCTTA:T	donor_gain	1.0000
11:95778817:CTTA:C	donor_loss	1.0000
11:95778817:CTTAC:C	donor_gain	1.0000
11:95778818:TTA:T	donor_gain	1.0000
11:95778819:TA:T	donor_gain	1.0000
11:95778820:A:AC	donor_gain	1.0000
11:95778820:A:C	donor_gain	1.0000
11:95778821:C:A	donor_loss	1.0000
11:95778821:C:CC	donor_gain	1.0000
11:95778821:C:G	donor_gain	1.0000
11:95778953:AGCTA:A	acceptor_gain	1.0000
11:95778954:GCTAC:G	acceptor_gain	1.0000
11:95778955:CTA:C	acceptor_gain	1.0000
11:95778955:CTACT:C	acceptor_gain	1.0000
11:95778956:TA:T	acceptor_gain	1.0000
11:95778957:AC:A	acceptor_loss	1.0000

AlphaMissense

2251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:95771634:A:G	L316P	1.000
11:95776013:A:G	L280P	1.000
11:95778874:A:G	L259P	1.000
11:95778895:A:G	L252S	1.000
11:95783217:T:A	R137S	1.000
11:95783217:T:G	R137S	1.000
11:95783225:A:C	Y135D	1.000
11:95783235:A:C	C131W	1.000
11:95783236:C:A	C131F	1.000
11:95783236:C:G	C131S	1.000
11:95783236:C:T	C131Y	1.000
11:95783237:A:G	C131R	1.000
11:95783237:A:T	C131S	1.000
11:95783239:A:G	L130P	1.000
11:95783241:C:A	W129C	1.000
11:95783241:C:G	W129C	1.000
11:95783243:A:G	W129R	1.000
11:95783243:A:T	W129R	1.000
11:95783244:G:C	C128W	1.000
11:95783245:C:A	C128F	1.000
11:95783245:C:G	C128S	1.000
11:95783245:C:T	C128Y	1.000
11:95783246:A:G	C128R	1.000
11:95783246:A:T	C128S	1.000
11:95783248:A:G	L127S	1.000
11:95786146:A:C	F112L	1.000
11:95786146:A:T	F112L	1.000
11:95786147:A:C	F112C	1.000
11:95786147:A:G	F112S	1.000
11:95786148:A:G	F112L	1.000

dbSNP variants (sampled 300 via entrez): RS1000024325 (11:95773529 T>C), RS1000116560 (11:95785659 A>C,G), RS1000246363 (11:95770932 T>G), RS1000416925 (11:95789934 G>A,T), RS1000505841 (11:95790645 C>T), RS1000532018 (11:95783136 T>C), RS1000642115 (11:95777265 G>A), RS1000718640 (11:95775708 TTC>T), RS1000722583 (11:95770585 A>C), RS1000771455 (11:95776163 A>C,T), RS1000878381 (11:95791091 G>A), RS1000997198 (11:95770072 G>A), RS1001395826 (11:95773282 T>C), RS1001437301 (11:95774118 A>G), RS1001444527 (11:95773606 C>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

20 associations (top):

Study	Trait	p-value
GCST005038_133	Allergic disease (asthma, hay fever or eczema)	2.000000e-11
GCST005973_11	White blood cell count	2.000000e-13
GCST005977_24	Monocyte count	4.000000e-10
GCST006950_4	Feeling worry	2.000000e-09
GCST006976_89	Macular thickness	5.000000e-09
GCST007094_180	Diastolic blood pressure	3.000000e-11
GCST007098_73	Diastolic blood pressure	5.000000e-06
GCST007098_74	Diastolic blood pressure	7.000000e-06
GCST007123_2	Multiple sclerosis and LDL levels (pleiotropy)	6.000000e-06
GCST007576_199	Chronotype	8.000000e-09
GCST009615_13	Triglyceride levels x loop diuretics use interaction	1.000000e-06
GCST009723_10	Vertical cup-disc ratio (adjusted for vertical disc diameter)	3.000000e-08
GCST009724_79	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-10
GCST010002_246	Refractive error	3.000000e-10
GCST010241_402	Apolipoprotein A1 levels	1.000000e-10
GCST010242_169	HDL cholesterol levels	2.000000e-11
GCST010396_16	Gut microbiota (bacterial taxa, hurdle binary method)	9.000000e-06
GCST011534_2	Sun-seeking behavior	4.000000e-09
GCST90011899_59	Aspartate aminotransferase levels	1.000000e-08
GCST90013442_18	Keratoconus	1.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0009589	worry measurement
EFO:0006336	diastolic blood pressure
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008328	chronotype measurement
EFO:0004530	triglyceride measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007874	gut microbiome measurement
EFO:0010729	sun exposure measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, decreases expression	3
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Arsenic	increases abundance, decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, increases expression	1
Demecolcine	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Ethyl Methanesulfonate	decreases expression	1
Fluorouracil	decreases expression	1
Hydrogen Peroxide	decreases expression	1

Clinical trials (associated diseases)

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