FAM53B

Summary

FAM53B (family with sequence similarity 53 member B, HGNC:28968) is a protein-coding gene on chromosome 10q26.13, encoding Protein FAM53B (Q14153). Acts as a regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) nuclear localization.

Involved in positive regulation of canonical Wnt signaling pathway. Located in nucleus.

Source: NCBI Gene 9679 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_014661

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28968
Approved symbol	FAM53B
Name	family with sequence similarity 53 member B
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	bA12J10.2, smp
Ensembl gene	ENSG00000189319
Ensembl biotype	protein_coding
OMIM	617289
Entrez	9679

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000280780, ENST00000337318, ENST00000392754, ENST00000870308, ENST00000870309, ENST00000870310, ENST00000952224, ENST00000952225, ENST00000952226, ENST00000952227

RefSeq mRNA: 1 — MANE Select: NM_014661 NM_014661

CCDS: CCDS7641

Canonical transcript exons

ENST00000337318 — 5 exons

Exon	Start	End
ENSE00001432503	124619292	124623604
ENSE00001825760	124744013	124744378
ENSE00003542605	124681607	124682379
ENSE00003562098	124696158	124696212
ENSE00003607391	124706636	124706887

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3826 / max 284.9707, expressed in 1667 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111855	4.5344	1320
111856	3.3376	1156
111852	3.1029	833
111851	0.8317	374
111857	0.7273	389
111854	0.5444	322
111853	0.3044	110

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	94.38	silver quality
ventricular zone	UBERON:0003053	93.86	gold quality
ganglionic eminence	UBERON:0004023	92.81	gold quality
granulocyte	CL:0000094	92.70	gold quality
gastrocnemius	UBERON:0001388	91.33	gold quality
type B pancreatic cell	CL:0000169	91.21	gold quality
muscle of leg	UBERON:0001383	90.45	gold quality
thymus	UBERON:0002370	89.88	gold quality
lymph node	UBERON:0000029	89.40	gold quality
middle frontal gyrus	UBERON:0002702	89.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.95	gold quality
muscle organ	UBERON:0001630	88.91	gold quality
skeletal muscle organ	UBERON:0014892	88.91	gold quality
apex of heart	UBERON:0002098	88.54	gold quality
blood	UBERON:0000178	88.43	gold quality
decidua	UBERON:0002450	88.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.05	gold quality
triceps brachii	UBERON:0001509	87.59	silver quality
inferior vagus X ganglion	UBERON:0005363	87.53	gold quality
spinal cord	UBERON:0002240	87.41	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	87.27	gold quality
ileal mucosa	UBERON:0000331	87.23	gold quality
tibial nerve	UBERON:0001323	87.09	gold quality
nasal cavity epithelium	UBERON:0005384	86.58	gold quality
corpus callosum	UBERON:0002336	86.53	gold quality
tonsil	UBERON:0002372	86.20	gold quality
leukocyte	CL:0000738	86.06	gold quality
sural nerve	UBERON:0015488	85.67	gold quality
skeletal muscle tissue	UBERON:0001134	85.48	gold quality
mononuclear cell	CL:0000842	85.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting FAM53B, 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-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6764-5P	99.75	67.89	2304

Literature-anchored findings (GeneRIF, showing 3)

• Strong candidate gene for age-related macular degeneration, ARMS2, (human 10q26.13). Conclusion is based on a massive expression data set for mouse (103 strains) and joint analysis of RetNet database. (PMID:19727342)
• First study to identify risk variants for cocaine dependence using GWAS; rs2629540 at the FAM53B identified as a risk factor in African- and European-Americans (PMID:23958962)
• The circ_FAM53B-miR-183-5p-CCDC6 axis modulates the malignant behaviors of papillary thyroid carcinoma cells. (PMID:35598218)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam53b	ENSDARG00000016156
mus_musculus	Fam53b	ENSMUSG00000030956
rattus_norvegicus	Fam53b	ENSRNOG00000061348

Paralogs (2): FAM53C (ENSG00000120709), FAM53A (ENSG00000174137)

Protein

Protein identifiers

Protein FAM53B — Q14153 (reviewed: Q14153)

Alternative names: Protein simplet

All UniProt accessions (1): Q14153

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) nuclear localization.

Subunit / interactions. Interacts with CTNNB1.

Subcellular location. Nucleus.

Tissue specificity. Detected in skeletal muscle, kidney, spleen, thyroid, testis, ovary, small intestine, colon and peripheral blood.

Similarity. Belongs to the FAM53 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14153-1	1	yes
Q14153-2	2

RefSeq proteins (1): NP_055476* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029356	FAM53	Family

Pfam: PF15242

UniProt features (13 total): modified residue 6, splice variant 2, chain 1, region of interest 1, sequence conflict 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14153-F1	52.88	0.00

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 (6): 118, 167, 169, 179, 212, 268

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 223 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, NKX25_02, TTTGTAG_MIR520D, MODULE_45, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, MAZ_Q6, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, MODULE_16, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, FOXO1_01, FOXD3_01, NKX61_01, GOBP_NUCLEAR_TRANSPORT, GTGCCTT_MIR506

GO Biological Process (4): protein import into nucleus (GO:0006606), Wnt signaling pathway (GO:0016055), regulation of canonical Wnt signaling pathway (GO:0060828), positive regulation of canonical Wnt signaling pathway (GO:0090263)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
canonical Wnt signaling pathway	2
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
cell surface receptor signaling pathway	1
regulation of Wnt signaling pathway	1
positive regulation of Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM53B	CNIH3	Q8TBE1	550
FAM53B	SNW1	Q13573	510
FAM53B	CYFIP2	Q96F07	461
FAM53B	KLK4	Q9Y5K2	444
FAM53B	MMP13	P45452	407
FAM53B	TXN2	Q99757	396
FAM53B	FZD10	Q9ULW2	396
FAM53B	ROCK2	O75116	394
FAM53B	GLO1	P78375	393
FAM53B	MMP3	P08254	390
FAM53B	MMP2	P08253	386
FAM53B	SERPINE1	P05121	383
FAM53B	MMP8	P22894	377
FAM53B	CDC42BPA	Q5VT25	375
FAM53B	NANOS2	P60321	371

IntAct

20 interactions, top by confidence:

A	B	Type	Score
FAM53B	YWHAZ	psi-mi:“MI:0915”(physical association)	0.710
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
FAM53B	SFN	psi-mi:“MI:0914”(association)	0.560
FAM53B	SFN	psi-mi:“MI:0915”(physical association)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FAM53B	CBY1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): FAM53B (Affinity Capture-MS), CBY1 (Affinity Capture-MS), FAM53B (Affinity Capture-RNA), FAM53B (Affinity Capture-RNA), FAM53B (Affinity Capture-MS), FAM53B (Two-hybrid), FAM53B (Two-hybrid), SFN (Affinity Capture-MS), FAM53B (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), YWHAZ (Affinity Capture-MS), YWHAE (Affinity Capture-MS), YWHAH (Affinity Capture-MS), ERP44 (Affinity Capture-MS), FAM53B (Affinity Capture-MS)

ESM2 similar proteins: A2RU30, A6NCL1, A9JRX0, D3YN49, D3ZDX9, D6RGH6, E9PV82, F1QN48, F1SLM8, F7BHS0, G3N1S4, H2M146, P01106, P06171, P0C0N9, P12525, P15171, P23999, P35805, Q05404, Q08B36, Q14140, Q14153, Q28C41, Q2T9X8, Q3U132, Q3URY2, Q3UZ45, Q5M9G5, Q5PQS2, Q5R8C5, Q5RBY6, Q5RKG1, Q5ZKN5, Q64210, Q6DF94, Q6NRH7, Q70YC5, Q7SXC6, Q7TNY7

Diamond homologs: E9PV82, F1QN48, H2M146, Q14153, Q29RM2, Q5R815, Q5ZKN5, Q6NSI3, Q8BGR5, Q8BXQ8, Q9NYF3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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
Activation of BAD and translocation to mitochondria	7	355.3×	6e-16
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	313.5×	9e-16
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	313.5×	9e-16
Activation of BH3-only proteins	7	231.7×	9e-15
RHO GTPases activate PKNs	7	148.0×	2e-13
Intrinsic Pathway for Apoptosis	7	136.7×	3e-13
FOXO-mediated transcription	5	112.0×	4e-09
SARS-CoV-1-host interactions	7	82.0×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	114.5×	3e-08
intracellular protein localization	8	52.3×	9e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2110 predictions. Top by Δscore:

Variant	Effect	Δscore
10:124623343:T:A	donor_gain	1.0000
10:124682386:C:CT	acceptor_gain	1.0000
10:124682386:CA:C	acceptor_gain	1.0000
10:124682387:A:C	acceptor_gain	1.0000
10:124744011:A:AC	donor_gain	1.0000
10:124744012:C:CC	donor_gain	1.0000
10:124623239:C:CA	donor_gain	0.9900
10:124623256:T:C	donor_gain	0.9900
10:124623600:CAGTT:C	acceptor_gain	0.9900
10:124623605:C:CC	acceptor_gain	0.9900
10:124682376:TTTT:T	acceptor_gain	0.9900
10:124682380:C:CC	acceptor_gain	0.9900
10:124682387:A:AC	acceptor_gain	0.9900
10:124682391:A:C	acceptor_gain	0.9900
10:124696213:C:CC	acceptor_gain	0.9900
10:124743536:T:TA	donor_gain	0.9900
10:124623263:A:AC	donor_gain	0.9800
10:124623263:AATGT:A	donor_gain	0.9800
10:124682377:TTTC:T	acceptor_loss	0.9800
10:124682381:T:A	acceptor_loss	0.9800
10:124682387:A:T	acceptor_gain	0.9800
10:124682391:A:AC	acceptor_gain	0.9800
10:124696211:TG:T	acceptor_gain	0.9800
10:124706699:TAGG:T	donor_gain	0.9800
10:124706700:AGGA:A	donor_gain	0.9800
10:124744177:T:TA	donor_gain	0.9800
10:124623604:TC:T	acceptor_loss	0.9700
10:124623605:C:CG	acceptor_loss	0.9700
10:124623605:C:T	acceptor_loss	0.9700
10:124681601:TCTTA:T	donor_loss	0.9700

AlphaMissense

2762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:124681667:C:A	R282S	0.999
10:124681667:C:G	R282S	0.999
10:124682099:C:A	W138C	0.999
10:124682099:C:G	W138C	0.999
10:124682101:A:G	W138R	0.999
10:124682101:A:T	W138R	0.999
10:124682125:A:G	W130R	0.999
10:124682125:A:T	W130R	0.999
10:124681668:C:G	R282T	0.998
10:124681670:T:A	K281N	0.998
10:124681670:T:G	K281N	0.998
10:124682123:C:A	W130C	0.998
10:124682123:C:G	W130C	0.998
10:124682173:A:G	C114R	0.998
10:124682179:G:T	R112S	0.998
10:124682180:C:A	K111N	0.998
10:124682180:C:G	K111N	0.998
10:124681614:A:G	M300T	0.997
10:124681616:C:A	K299N	0.997
10:124681616:C:G	K299N	0.997
10:124681668:C:A	R282M	0.997
10:124681715:G:C	S266R	0.996
10:124681715:G:T	S266R	0.996
10:124681717:T:G	S266R	0.996
10:124682012:G:C	S167R	0.996
10:124682012:G:T	S167R	0.996
10:124682014:T:G	S167R	0.996
10:124682069:G:C	S148R	0.996
10:124682069:G:T	S148R	0.996
10:124682071:T:G	S148R	0.996

dbSNP variants (sampled 300 via entrez): RS1000002863 (10:124693545 G>C), RS1000004500 (10:124670168 AC>A), RS1000005709 (10:124720669 T>C), RS1000014999 (10:124735620 C>T), RS1000031808 (10:124741409 C>A), RS1000044356 (10:124683006 G>A), RS1000062171 (10:124620590 T>A,C), RS1000081656 (10:124736902 C>G,T), RS1000090092 (10:124697411 G>A), RS1000094487 (10:124620871 T>G), RS1000105296 (10:124676783 C>T), RS1000147265 (10:124741092 T>G), RS1000179733 (10:124637562 C>A), RS1000193606 (10:124624015 G>A), RS1000210735 (10:124661922 T>C)

Disease associations

OMIM: gene MIM:617289 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST001762_342	Obesity-related traits	8.000000e-06
GCST002142_3	Cocaine dependence	4.000000e-08
GCST002142_8	Cocaine dependence	1.000000e-06
GCST003983_19	Male-pattern baldness	1.000000e-12
GCST004131_12	Inflammatory bowel disease	1.000000e-09
GCST004132_94	Crohn’s disease	3.000000e-06
GCST004133_33	Ulcerative colitis	1.000000e-06
GCST004599_12	Mean platelet volume	8.000000e-09
GCST004610_116	White blood cell count	5.000000e-09
GCST004618_32	White blood cell count (basophil)	5.000000e-10
GCST005116_14	Male-pattern baldness	3.000000e-17
GCST006661_312	Male-pattern baldness	6.000000e-21
GCST006870_6	Hippocampal tail volume	3.000000e-14
GCST006871_8	Total hippocampal volume	1.000000e-15
GCST006878_1	Dentate gyrus molecular layer volume (corrected for total hippocampal volume)	4.000000e-12
GCST006887_2	Hippocampal subfield CA1 volume	1.000000e-09
GCST006888_1	Hippocampal subfield CA3 volume	3.000000e-12
GCST006889_4	Hippocampal subfield CA4 volume	6.000000e-15
GCST006890_3	Dentate gyrus granule cell layer volume	9.000000e-15
GCST006891_2	Dentate gyrus molecular layer volume	2.000000e-10
GCST007344_87	Estimated glomerular filtration rate	5.000000e-10
GCST008745_77	Estimated glomerular filtration rate in non-diabetics	3.000000e-10
GCST008747_122	Estimated glomerular filtration rate	1.000000e-13
GCST009391_724	Metabolite levels	4.000000e-07
GCST010703_92	Brain morphology (MOSTest)	4.000000e-63
GCST012226_336	Waist circumference adjusted for body mass index	5.000000e-08
GCST90002379_85	Basophil count	1.000000e-20
GCST90002380_98	Basophil percentage of white cells	1.000000e-10
GCST90002382_198	Eosinophil percentage of white cells	1.000000e-14
GCST90002388_528	Lymphocyte count	3.000000e-20

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0005035	hippocampal volume
EFO:0009394	hippocampal CA1 volume
EFO:0009395	hippocampal CA3 volume
EFO:0009396	hippocampal CA4 volume
EFO:0009774	serine measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007992	basophil percentage of leukocytes
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	decreases methylation, decreases expression	2
Valproic Acid	decreases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
benzo(e)pyrene	increases methylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	decreases methylation	1
Acetaminophen	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases expression, decreases expression, affects response to substance	1
Methapyrilene	increases methylation	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Quercetin	increases phosphorylation	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	increases expression	1

Clinical trials (associated diseases)

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