FAM168A

Summary

FAM168A (family with sequence similarity 168 member A, HGNC:28999) is a protein-coding gene on chromosome 11q13.4, encoding Protein FAM168A (Q92567). In cancer context, protects cells from induced-DNA damage and apoptosis.

Involved in positive regulation of base-excision repair.

Source: NCBI Gene 23201 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_015159

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28999
Approved symbol	FAM168A
Name	family with sequence similarity 168 member A
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	TCRP1
Ensembl gene	ENSG00000054965
Ensembl biotype	protein_coding
OMIM	616316
Entrez	23201

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000064778, ENST00000356467, ENST00000432223, ENST00000450446, ENST00000632101, ENST00000876784, ENST00000876785, ENST00000876786, ENST00000876787, ENST00000930863

RefSeq mRNA: 3 — MANE Select: NM_015159 NM_001286050, NM_001286051, NM_015159

CCDS: CCDS41689, CCDS66165, CCDS73346

Canonical transcript exons

ENST00000356467 — 8 exons

Exon	Start	End
ENSE00000739828	73411394	73411536
ENSE00000797503	73407513	73407643
ENSE00000797504	73409487	73409661
ENSE00000797505	73419874	73419999
ENSE00001103286	73430690	73430770
ENSE00001103301	73597923	73598112
ENSE00002278677	73400487	73406744
ENSE00003483884	73468405	73468492

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 96.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.7940 / max 386.9795, expressed in 1794 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121256	32.9187	1788
121257	3.4597	1500
121255	1.1545	518
121258	0.8366	433
206379	0.4782	245
206378	0.3543	170
121254	0.2918	133
121253	0.2196	88
121252	0.0698	33
121250	0.0108	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.42	gold quality
ganglionic eminence	UBERON:0004023	95.42	gold quality
lateral globus pallidus	UBERON:0002476	95.07	gold quality
postcentral gyrus	UBERON:0002581	94.75	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.65	gold quality
prefrontal cortex	UBERON:0000451	94.53	gold quality
primary visual cortex	UBERON:0002436	94.33	gold quality
pons	UBERON:0000988	94.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.27	gold quality
superior frontal gyrus	UBERON:0002661	94.16	gold quality
ventricular zone	UBERON:0003053	94.14	gold quality
substantia nigra pars compacta	UBERON:0001965	94.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.01	gold quality
subthalamic nucleus	UBERON:0001906	93.84	gold quality
parietal lobe	UBERON:0001872	93.78	gold quality
right frontal lobe	UBERON:0002810	93.78	gold quality
spinal cord	UBERON:0002240	93.75	gold quality
occipital lobe	UBERON:0002021	93.61	gold quality
neocortex	UBERON:0001950	93.60	gold quality
frontal cortex	UBERON:0001870	93.56	gold quality
frontal lobe	UBERON:0016525	93.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.40	gold quality
cingulate cortex	UBERON:0003027	93.36	gold quality
cerebral cortex	UBERON:0000956	93.30	gold quality
amygdala	UBERON:0001876	93.24	gold quality
anterior cingulate cortex	UBERON:0009835	93.24	gold quality
inferior olivary complex	UBERON:0002127	93.11	gold quality
telencephalon	UBERON:0001893	92.94	gold quality
temporal lobe	UBERON:0001871	92.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

331 targeting FAM168A, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
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

Literature-anchored findings (GeneRIF, showing 7)

• Data suggest that TCRP1 (EF363480) might be a novel molecular target to develop agents to reverse cisplatin-induced chemoresistance. (PMID:21334329)
• siRNA-mediated knockdown of TCRP1 and MT1X was found to sensitize cells to cisplatin, leading to increased apoptosis and inhibition of cell proliferation (PMID:23251525)
• Data show that tongue cancer resistance-associated protein 1 (TCRP1) contributes to cisplatin (DDP) resistance via the increased expression of DNA polymerase beta subunit (Pol beta) in lung cancer cells. (PMID:25260657)
• Combined, these findings suggest that c-Myc could transcriptionally regulate TCRP1 in cell lines and clinical samples and identified the c-Myc-TCRP1 axis as a negative biomarker of prognosis in tongue and lung cancers. (PMID:28623290)
• Our results highlight that hyper-methylation of miR-493CpG island might play important roles in the development of lung cancer chemo-resistance by targeting TCRP1, which might be used as a potential therapeutic target in preventing the chemo-resistance of lung cancer. (PMID:28859669)
• FAM168A involved in the regulation of AKT1/NFkappaB signaling pathway and cell cycle in chronic myeloid leukemia. (PMID:31291942)
• TCRP1 induces tamoxifen resistance by promoting the activation of SGK1 in MCF7 cells. (PMID:32323833)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam168a	ENSDARG00000098832
mus_musculus	Fam168a	ENSMUSG00000029461
rattus_norvegicus	Fam168a	ENSRNOG00000018873

Paralogs (1): FAM168B (ENSG00000152102)

Protein

Protein identifiers

Protein FAM168A — Q92567 (reviewed: Q92567)

Alternative names: Tongue cancer chemotherapy resistance-associated protein 1

All UniProt accessions (1): Q92567

UniProt curated annotations — full annotation on UniProt →

Function. In cancer context, protects cells from induced-DNA damage and apoptosis. Acts, at least in part, through PI3K/AKT/NFKB signaling pathway and by preventing POLB degradation. Decreases POLB ubiquitation and stabilizes its protein levels.

Subunit / interactions. Interacts with POLB. Interacts with AKT1 and MT1X. May interact with FAM168B.

Disease relevance. Associated with cisplatin (DDP)-resistance and radioresistance in the treatment of lung cancer as well as oral squamous cell carcinoma and poor clinical outcome in patients.

Similarity. Belongs to the FAM168 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92567-1	1	yes
Q92567-2	2
Q92567-3	3

RefSeq proteins (3): NP_001272979, NP_001272980, NP_055974* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029247	FAM168A/MANI	Family

Pfam: PF14944

UniProt features (6 total): modified residue 2, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92567-F1	45.39	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 (2): 1, 102

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, BROWNE_HCMV_INFECTION_6HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, chr11q13, GOBP_REGULATION_OF_DNA_REPAIR, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, GOBP_DNA_METABOLIC_PROCESS, GOBP_DNA_REPAIR

GO Biological Process (1): positive regulation of base-excision repair (GO:1905053)

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
base-excision repair	1
positive regulation of DNA repair	1
regulation of base-excision repair	1
binding	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM168A	MT1X	P80297	544
FAM168A	AKT1	P31749	507
FAM168A	GAGE12H	A6NDE8	403
FAM168A	FCHSD2	O94868	402
FAM168A	KLHDC8B	Q8IXV7	366
FAM168A	SEL1L2	Q5TEA6	362
FAM168A	GAGE12B	A1L429	353
FAM168A	TMEM161A	Q9NX61	341
FAM168A	STARD10	Q9Y365	329
FAM168A	RIOK2	Q9BVS4	308
FAM168A	PLEKHB1	Q9UF11	308
FAM168A	DNAAF9	Q5TEA3	301
FAM168A	ARAP1	Q96P48	298
FAM168A	GALNTL6	Q49A17	296
FAM168A	EPB41L4B	Q9H329	276
FAM168A	ZNF337	Q9Y3M9	276

IntAct

84 interactions, top by confidence:

A	B	Type	Score
FAM168A	SS18L1	psi-mi:“MI:0915”(physical association)	0.670
UBE2V1	FAM168A	psi-mi:“MI:0915”(physical association)	0.670
FAM168A	SF1	psi-mi:“MI:0915”(physical association)	0.670
FAM168A	UBASH3B	psi-mi:“MI:0915”(physical association)	0.670
OTUB2	FAM168A	psi-mi:“MI:0915”(physical association)	0.670
FAM168A	OTUB2	psi-mi:“MI:0915”(physical association)	0.670
FAM168A	UBE2V1	psi-mi:“MI:0915”(physical association)	0.670
UBASH3B	FAM168A	psi-mi:“MI:0915”(physical association)	0.670
SF1	FAM168A	psi-mi:“MI:0915”(physical association)	0.670
SS18L1	FAM168A	psi-mi:“MI:0915”(physical association)	0.670
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
VPS37C	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
FAM168A	PRR20C	psi-mi:“MI:0915”(physical association)	0.560
FAM168A	DTX2	psi-mi:“MI:0915”(physical association)	0.560
SNRPC	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
C1orf94	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
SMAP2	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
FAM168A	DAB1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (166): FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), FAM168A (Two-hybrid), SS18L1 (Two-hybrid), VPS37C (Two-hybrid), KLHL42 (Two-hybrid), SMAP2 (Two-hybrid)

ESM2 similar proteins: A0JNC2, A1KXE4, A8E639, A8MV65, D4AEP3, E3X5D6, P05411, P12981, P18870, P54864, P60486, Q08BY2, Q0IHC4, Q0VFP2, Q14157, Q15032, Q15038, Q157S1, Q16656, Q3LRZ1, Q3T0A9, Q3T0K9, Q3U182, Q4R5H7, Q53ET0, Q58D45, Q5BJ83, Q5R526, Q5RDV6, Q5U2U6, Q5XIH2, Q5ZIS9, Q68ED7, Q6PEH8, Q7PXU6, Q80TM6, Q80X50, Q80XQ8, Q8AVW3, Q8BGZ2

Diamond homologs: A1KXE4, A8E639, D4AEP3, Q08BY2, Q0IHC4, Q0VFP2, Q80XQ8, Q8BGZ2, Q92567

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2760 predictions. Top by Δscore:

Variant	Effect	Δscore
11:73406740:CAGAT:C	acceptor_gain	1.0000
11:73406741:AGATC:A	acceptor_loss	1.0000
11:73406742:GAT:G	acceptor_gain	1.0000
11:73406743:ATCT:A	acceptor_loss	1.0000
11:73406744:TC:T	acceptor_loss	1.0000
11:73406745:C:CC	acceptor_gain	1.0000
11:73407511:A:AC	donor_gain	1.0000
11:73407512:C:CC	donor_gain	1.0000
11:73409481:CCTCA:C	donor_loss	1.0000
11:73409483:TCAC:T	donor_loss	1.0000
11:73409484:CA:C	donor_loss	1.0000
11:73409485:ACCT:A	donor_loss	1.0000
11:73409486:CCTG:C	donor_gain	1.0000
11:73409658:CTCC:C	acceptor_gain	1.0000
11:73409659:TCCC:T	acceptor_loss	1.0000
11:73409660:CC:C	acceptor_gain	1.0000
11:73409660:CCCTG:C	acceptor_loss	1.0000
11:73409661:CC:C	acceptor_gain	1.0000
11:73409661:CCTGG:C	acceptor_loss	1.0000
11:73409662:CTG:C	acceptor_loss	1.0000
11:73419872:A:AC	donor_gain	1.0000
11:73419873:C:CC	donor_gain	1.0000
11:73430684:CCTTA:C	donor_loss	1.0000
11:73430685:CTTA:C	donor_loss	1.0000
11:73430686:TTACC:T	donor_loss	1.0000
11:73430687:TACC:T	donor_loss	1.0000
11:73430688:A:T	donor_loss	1.0000
11:73430766:GTAAC:G	acceptor_gain	1.0000
11:73430767:TAAC:T	acceptor_gain	1.0000
11:73430768:AAC:A	acceptor_gain	1.0000

AlphaMissense

1502 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:73409597:A:T	V171D	0.999
11:73409600:A:T	V170D	0.999
11:73409606:G:A	T168I	0.999
11:73409609:T:C	H167R	0.999
11:73409610:G:C	H167D	0.999
11:73409613:G:C	H166D	0.999
11:73409615:A:C	I165S	0.999
11:73409615:A:G	I165T	0.999
11:73409615:A:T	I165N	0.999
11:73409608:A:C	H167Q	0.998
11:73409608:A:T	H167Q	0.998
11:73409618:A:T	V164D	0.998
11:73409603:G:T	T169K	0.997
11:73409609:T:A	H167L	0.997
11:73409610:G:A	H167Y	0.997
11:73409612:T:C	H166R	0.997
11:73409523:C:G	G196R	0.996
11:73409584:G:C	S175R	0.996
11:73409584:G:T	S175R	0.996
11:73409586:T:G	S175R	0.996
11:73409603:G:C	T169R	0.996
11:73409610:G:T	H167N	0.996
11:73411424:A:C	S139R	0.996
11:73411424:A:T	S139R	0.996
11:73411426:T:G	S139R	0.996
11:73407536:A:G	W244R	0.995
11:73407536:A:T	W244R	0.995
11:73409495:A:T	M205K	0.995
11:73409504:G:A	T202I	0.995
11:73409609:T:G	H167P	0.995

dbSNP variants (sampled 300 via entrez): RS1000009170 (11:73521151 T>C), RS1000011877 (11:73431908 C>T), RS1000047644 (11:73568145 A>C), RS1000104570 (11:73437296 T>A,C), RS1000107295 (11:73578664 C>G), RS1000131492 (11:73532901 ACT>A), RS1000153760 (11:73404468 T>C), RS1000164012 (11:73532536 A>G), RS1000173766 (11:73442222 T>A,G), RS1000194577 (11:73579990 T>C), RS1000230092 (11:73451054 G>A), RS1000231048 (11:73495803 A>C,G), RS1000234023 (11:73495657 A>G), RS1000241104 (11:73495502 C>T), RS1000242874 (11:73458990 T>C)

Disease associations

OMIM: gene MIM:616316 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001784_16	Pulmonary function (smoking interaction)	4.000000e-07
GCST001784_38	Pulmonary function (smoking interaction)	3.000000e-07
GCST006482_1	Lung function (FEV1/FVC)	3.000000e-08
GCST006482_2	Lung function (FEV1/FVC)	5.000000e-06
GCST006627_88	Diastolic blood pressure	5.000000e-09
GCST006979_410	Heel bone mineral density	3.000000e-09
GCST008155_61	Waist-hip ratio	6.000000e-07
GCST010002_243	Refractive error	1.000000e-13
GCST010241_304	Apolipoprotein A1 levels	1.000000e-08
GCST90002402_355	Platelet count	8.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0004343	waist-hip ratio
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004309	platelet count

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
Valproic Acid	affects cotreatment, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	3
Cisplatin	increases cleavage, affects cotreatment, increases expression, decreases reaction, decreases response to substance	3
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
bisphenol A	increases methylation	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, decreases response to substance, increases cleavage	1
perfluoro-n-nonanoic acid	decreases expression	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases reaction, decreases response to substance, increases cleavage	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Lead	affects expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XN66	HAP1 FAM168A (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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