FAM162A

Summary

FAM162A (family with sequence similarity 162 member A, HGNC:17865) is a protein-coding gene on chromosome 3q21.1, encoding Protein FAM162A (Q96A26). Proposed to be involved in regulation of apoptosis; the exact mechanism may differ between cell types/tissues.

Involved in cellular response to hypoxia; positive regulation of apoptotic process; and positive regulation of release of cytochrome c from mitochondria. Located in cytosol and mitochondrion.

Source: NCBI Gene 26355 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 30 total
• Druggable target: yes
• MANE Select transcript: NM_014367

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17865
Approved symbol	FAM162A
Name	family with sequence similarity 162 member A
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	E2IG5, HGTD-P
Ensembl gene	ENSG00000114023
Ensembl biotype	protein_coding
OMIM	608017
Entrez	26355

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000232125, ENST00000469967, ENST00000477892, ENST00000684791, ENST00000685650, ENST00000686446, ENST00000686831, ENST00000687114, ENST00000688631, ENST00000688794, ENST00000688900, ENST00000689215, ENST00000692876, ENST00000693245

RefSeq mRNA: 1 — MANE Select: NM_014367 NM_014367

CCDS: CCDS43139

Canonical transcript exons

ENST00000477892 — 5 exons

Exon	Start	End
ENSE00000776488	122404258	122404363
ENSE00000823737	122402760	122402882
ENSE00001363323	122407281	122407389
ENSE00001865253	122409739	122412334
ENSE00001931914	122384182	122384299

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 91.3911 / max 786.2184, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38233	87.2612	1826
38232	4.1299	1589

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	99.76	gold quality
colonic mucosa	UBERON:0000317	99.74	gold quality
tongue squamous epithelium	UBERON:0006919	99.58	gold quality
mammalian vulva	UBERON:0000997	99.33	gold quality
heart right ventricle	UBERON:0002080	99.31	gold quality
gingiva	UBERON:0001828	99.18	gold quality
oral cavity	UBERON:0000167	99.17	gold quality
gingival epithelium	UBERON:0001949	99.11	gold quality
myocardium	UBERON:0002349	99.11	gold quality
mucosa of transverse colon	UBERON:0004991	99.09	gold quality
left ventricle myocardium	UBERON:0006566	99.09	gold quality
penis	UBERON:0000989	99.04	gold quality
ileal mucosa	UBERON:0000331	98.98	gold quality
pharyngeal mucosa	UBERON:0000355	98.94	gold quality
cervix epithelium	UBERON:0004801	98.90	gold quality
cartilage tissue	UBERON:0002418	98.86	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.85	gold quality
biceps brachii	UBERON:0001507	98.83	gold quality
body of tongue	UBERON:0011876	98.81	gold quality
cervix squamous epithelium	UBERON:0006922	98.72	gold quality
vastus lateralis	UBERON:0001379	98.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.69	gold quality
vena cava	UBERON:0004087	98.62	gold quality
squamous epithelium	UBERON:0006914	98.59	gold quality
upper arm skin	UBERON:0004263	98.57	gold quality
rectum	UBERON:0001052	98.48	gold quality
quadriceps femoris	UBERON:0001377	98.44	gold quality
triceps brachii	UBERON:0001509	98.43	gold quality
epithelium of esophagus	UBERON:0001976	98.43	gold quality
diaphragm	UBERON:0001103	98.39	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	852.31
E-GEOD-125970	yes	47.88
E-ANND-3	yes	13.34
E-MTAB-8271	yes	6.37
E-MTAB-6524	no	1022.40
E-MTAB-6819	no	1005.36
E-ENAD-21	no	766.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A

miRNA regulators (miRDB)

21 targeting FAM162A, 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-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-5579-5P	96.32	68.54	730
HSA-MIR-5681B	94.82	69.30	514

Literature-anchored findings (GeneRIF, showing 4)

• Data indicate that HGTD-P is a new hypoxia-inducible factor 1 alpha-responsive proapoptotic molecule that activates mitochondrial apoptotic cascades. (PMID:15082785)
• Heat shock protein 90 physically interacts with HGTD-P. (PMID:16698020)
• human growth and transformation-dependent protein expression is a common occurrence during the progression from a normal gastric mucosa to an intestinal-type carcinoma and may be associated with tumor cell proliferation activity (PMID:19269009)
• Expression and clinicopathological significance of human growth and transformation-dependent protein (HGTD-P) in uterine cervical cancer (PMID:20840676)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam162a	ENSMUSG00000003955
rattus_norvegicus	Fam162a	ENSRNOG00000002255
rattus_norvegicus		ENSRNOG00000073648
drosophila_melanogaster	CG9231	FBGN0036887
caenorhabditis_elegans		WBGENE00010879

Paralogs (1): FAM162B (ENSG00000183807)

Protein

Protein identifiers

Protein FAM162A — Q96A26 (reviewed: Q96A26)

Alternative names: E2-induced gene 5 protein, Growth and transformation-dependent protein

All UniProt accessions (8): Q96A26, A0A8I5KQT5, A0A8I5KUL7, A0A8I5KUT6, A0A8I5KW67, A0A8I5QJA3, E9PH05, F8W7Q4

UniProt curated annotations — full annotation on UniProt →

Function. Proposed to be involved in regulation of apoptosis; the exact mechanism may differ between cell types/tissues. May be involved in hypoxia-induced cell death of transformed cells implicating cytochrome C release and caspase activation (such as CASP9) and inducing mitochondrial permeability transition. May be involved in hypoxia-induced cell death of neuronal cells probably by promoting release of AIFM1 from mitochondria to cytoplasm and its translocation to the nucleus; however, the involvement of caspases has been reported conflictingly.

Subunit / interactions. Interacts with HSP90AB1; HSP90AB1 is essential for FAM162A mitochondrial localization and pro-apoptotic activity. Interacts with VDAC2; the interaction is probably involved in inducing mitochondrial permeability transition.

Subcellular location. Mitochondrion membrane.

Induction. By 17-beta-estradiol. By hypoxia.

Similarity. Belongs to the UPF0389 family.

RefSeq proteins (1): NP_055182* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009432	DUF1075	Family

Pfam: PF06388

UniProt features (4 total): chain 1, transmembrane region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A26-F1	64.21	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 250 (showing top): PAX4_01, GGGNRMNNYCAT_UNKNOWN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, MENSE_HYPOXIA_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_CYTOCHROME_C_FROM_MITOCHONDRIA, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REGULATION_OF_MITOCHONDRION_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS

GO Biological Process (5): positive regulation of apoptotic process (GO:0043065), neuron apoptotic process (GO:0051402), cellular response to hypoxia (GO:0071456), positive regulation of release of cytochrome c from mitochondria (GO:0090200), apoptotic process (GO:0006915)

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

GO Cellular Component (4): mitochondrion (GO:0005739), cytosol (GO:0005829), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
cytoplasm	2
cellular anatomical structure	2
regulation of apoptotic process	1
positive regulation of programmed cell death	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
release of cytochrome c from mitochondria	1
positive regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
binding	1
intracellular membrane-bounded organelle	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM162A	CMC2	Q9NRP2	599
FAM162A	NSL1	Q96IY1	580
FAM162A	AWAT2	Q6E213	507
FAM162A	TMEM107	Q6UX40	450
FAM162A	NXT2	Q9NPJ8	448
FAM162A	ARLN	Q8WVX3	446
FAM162A	FBXO8	Q9NRD0	445
FAM162A	ENY2	Q9NPA8	432
FAM162A	FUNDC2	Q9BWH2	416
FAM162A	TMEM65	Q6PI78	408
FAM162A	SLC12A7	Q9Y666	402
FAM162A	ALB	P02768	402
FAM162A	SPINT2	O43291	398
FAM162A	SPINT1	O43278	397
FAM162A	PECAM1	P16284	383

IntAct

79 interactions, top by confidence:

A	B	Type	Score
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
ASPH	STXBP3	psi-mi:“MI:0914”(association)	0.640
HSP90AB1	FAM162A	psi-mi:“MI:0915”(physical association)	0.540
FAM162A	HSP90AB1	psi-mi:“MI:0403”(colocalization)	0.540
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
rep	AGPS	psi-mi:“MI:0914”(association)	0.530
GHITM	MFN2	psi-mi:“MI:0914”(association)	0.530
ATP1A3	AGPAT2	psi-mi:“MI:0914”(association)	0.530
VDAC2	FAM162A	psi-mi:“MI:0915”(physical association)	0.520
FAM162A	VDAC2	psi-mi:“MI:0915”(physical association)	0.520
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PCDHA12	KLRG2	psi-mi:“MI:0914”(association)	0.350
CTNNA3	ARVCF	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
RAB5A	PSMD14	psi-mi:“MI:0914”(association)	0.350
rep	STXBP3	psi-mi:“MI:0914”(association)	0.350
rep	CEBPZOS	psi-mi:“MI:0914”(association)	0.350

BioGRID (95): FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-RNA), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-Western), VDAC1 (Affinity Capture-Western), FAM162A (Affinity Capture-MS), FAM162A (Affinity Capture-MS), FAM162A (Co-fractionation)

ESM2 similar proteins: A1XQT2, A3KP48, A8KB87, A8WGU8, O09111, O43674, O49313, O74988, O93980, P00424, P00425, P09669, P0DKM0, P11950, P53077, P80971, Q02376, Q02380, Q0MQ88, Q0MQD6, Q0MQD7, Q0MQD8, Q0MQJ3, Q290M9, Q29DG0, Q2NKR7, Q3T0E3, Q4QQV3, Q4R4E0, Q5R504, Q5R7J0, Q6CCF6, Q6CHT7, Q6CK73, Q6CLM9, Q6DQX6, Q6FW43, Q75FA7, Q7JX57, Q7YRK3

Diamond homologs: A3KP48, A6QPI4, Q29DG0, Q2NKR7, Q4QQV3, Q5R504, Q5T6X4, Q96A26, Q9CX19, Q9D6U8, Q9VW12

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HIF1A	“up-regulates quantity by expression”	FAM162A	“transcriptional regulation”
FAM162A	“up-regulates activity”	VDAC1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1058 predictions. Top by Δscore:

Variant	Effect	Δscore
3:122384296:GCAG:G	donor_gain	1.0000
3:122384298:AG:A	donor_loss	1.0000
3:122402883:G:GG	donor_gain	1.0000
3:122404359:GTCTC:G	donor_gain	1.0000
3:122404364:G:GG	donor_gain	1.0000
3:122407273:A:AG	acceptor_gain	1.0000
3:122407278:TAG:T	acceptor_loss	1.0000
3:122407279:A:T	acceptor_loss	1.0000
3:122407279:AGGTT:A	acceptor_gain	1.0000
3:122407280:GGTTG:G	acceptor_gain	1.0000
3:122407387:AAG:A	donor_loss	1.0000
3:122407389:GGT:G	donor_loss	1.0000
3:122407391:T:A	donor_loss	1.0000
3:122402755:TTTA:T	acceptor_loss	0.9900
3:122402756:TTAGG:T	acceptor_loss	0.9900
3:122402757:TA:T	acceptor_loss	0.9900
3:122402759:GGAA:G	acceptor_gain	0.9900
3:122402862:A:T	donor_gain	0.9900
3:122402878:ATCCC:A	donor_gain	0.9900
3:122402879:TCCC:T	donor_gain	0.9900
3:122402879:TCCCG:T	donor_loss	0.9900
3:122402881:CC:C	donor_gain	0.9900
3:122402882:CG:C	donor_loss	0.9900
3:122402883:GTAAG:G	donor_loss	0.9900
3:122402884:T:G	donor_loss	0.9900
3:122404253:CATA:C	acceptor_loss	0.9900
3:122404255:TA:T	acceptor_loss	0.9900
3:122404256:A:AG	acceptor_gain	0.9900
3:122404256:AGGC:A	acceptor_loss	0.9900
3:122404257:G:C	acceptor_loss	0.9900

AlphaMissense

1004 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:122404329:T:C	F77L	0.993
3:122404331:C:A	F77L	0.993
3:122404331:C:G	F77L	0.993
3:122407327:A:C	S104R	0.991
3:122407329:C:A	S104R	0.991
3:122407329:C:G	S104R	0.991
3:122407360:T:C	C115R	0.989
3:122404330:T:C	F77S	0.985
3:122404360:T:A	V87D	0.982
3:122407300:G:C	A95P	0.979
3:122407349:C:A	T111K	0.975
3:122404348:T:C	I83T	0.974
3:122407358:G:A	G114E	0.974
3:122407381:G:C	G122R	0.974
3:122407386:G:C	K123N	0.973
3:122407386:G:T	K123N	0.973
3:122407343:C:A	A109D	0.972
3:122407382:G:A	G122D	0.972
3:122407338:G:A	M107I	0.970
3:122407338:G:C	M107I	0.970
3:122407338:G:T	M107I	0.970
3:122407352:T:A	V112E	0.970
3:122407357:G:A	G114R	0.970
3:122407357:G:C	G114R	0.970
3:122404348:T:G	I83S	0.967
3:122407381:G:T	G122C	0.967
3:122409739:G:C	A125P	0.967
3:122404330:T:G	F77C	0.966
3:122407349:C:G	T111R	0.966
3:122404312:T:C	L71P	0.965

dbSNP variants (sampled 300 via entrez): RS1000041500 (3:122411725 T>G), RS1000111323 (3:122384564 C>A), RS1000434523 (3:122409959 G>A,T), RS1000500148 (3:122385661 A>T), RS1000544319 (3:122384250 G>A,C,T), RS1000592807 (3:122404979 C>T), RS1000726192 (3:122392048 G>A), RS1000742397 (3:122411861 T>C), RS1000807101 (3:122410195 T>C), RS1000843751 (3:122384109 C>A,T), RS1000977338 (3:122390187 A>G,T), RS1001091971 (3:122398098 T>C), RS1001174774 (3:122411511 A>G), RS1001493663 (3:122390232 G>A), RS1001602327 (3:122393806 G>A)

Disease associations

OMIM: gene MIM:608017 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000769_5	Calcium levels	2.000000e-22
GCST004956_1	Risky sexual behaviors (alcohol dependence interaction)	5.000000e-08
GCST007094_136	Diastolic blood pressure	2.000000e-08
GCST011657_1	C-reactive protein levels	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0006336	diastolic blood pressure
EFO:0004458	C-reactive protein measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067146 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	7
Cyclosporine	decreases expression	4
methylmercuric chloride	decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	affects expression, increases expression	2
sodium arsenite	increases abundance, increases expression, decreases expression	2
nickel sulfate	decreases expression, increases expression	2
entinostat	affects cotreatment, increases expression	2
bisphenol S	affects expression, affects cotreatment, increases expression	2
Cisplatin	decreases expression, increases expression	2
Doxorubicin	increases expression, affects expression	2
Oxygen	increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chloride	decreases reaction, increases expression	1
cobaltous chloride	increases expression, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
1-aminomethylphosphonic acid	decreases expression	1
epigallocatechin gallate	increases expression, decreases expression, affects cotreatment	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651404	Binding	Binding affinity to human FAM162A incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2WV	Abcam HEK293T FAM162A KO	Transformed cell line	Female

Clinical trials (associated diseases)

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