FAIM

Summary

FAIM (Fas apoptotic inhibitory molecule, HGNC:18703) is a protein-coding gene on chromosome 3q22.3, encoding Fas apoptotic inhibitory molecule 1 (Q9NVQ4). Plays a role as an inducible effector molecule that mediates Fas resistance produced by surface Ig engagement in B cells.

The protein encoded by this gene protects against death receptor-triggered apoptosis and regulates B-cell signaling and differentiation. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55179 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001033031

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18703
Approved symbol	FAIM
Name	Fas apoptotic inhibitory molecule
Location	3q22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10582, FAIM1
Ensembl gene	ENSG00000158234
Ensembl biotype	protein_coding
OMIM	617535
Entrez	55179

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 retained_intron

ENST00000338446, ENST00000360570, ENST00000393034, ENST00000393035, ENST00000464668, ENST00000464912, ENST00000470889, ENST00000479848, ENST00000491175, ENST00000869302, ENST00000869303, ENST00000928205, ENST00000944527, ENST00000944528, ENST00000944529

RefSeq mRNA: 4 — MANE Select: NM_001033031 NM_001033030, NM_001033031, NM_001033032, NM_018147

CCDS: CCDS3103, CCDS33864, CCDS33865

Canonical transcript exons

ENST00000360570 — 6 exons

Exon	Start	End
ENSE00001382953	138629107	138629156
ENSE00001403747	138608771	138608937
ENSE00001495226	138619711	138619770
ENSE00001829955	138632930	138633376
ENSE00003474790	138622188	138622416
ENSE00003477371	138621407	138621539

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 96.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.0365 / max 221.5980, expressed in 1735 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38801	10.3660	1654
38802	3.4901	1392
38800	0.6640	420
202947	0.5031	279
38804	0.0082	3
38803	0.0052	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	96.09	gold quality
right uterine tube	UBERON:0001302	95.54	gold quality
body of pancreas	UBERON:0001150	94.88	gold quality
epithelium of bronchus	UBERON:0002031	94.04	gold quality
seminal vesicle	UBERON:0000998	93.93	gold quality
bronchus	UBERON:0002185	93.47	gold quality
calcaneal tendon	UBERON:0003701	92.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.43	gold quality
pancreas	UBERON:0001264	91.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.23	gold quality
spinal cord	UBERON:0002240	91.02	gold quality
endometrium	UBERON:0001295	90.92	gold quality
palpebral conjunctiva	UBERON:0001812	90.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.92	gold quality
tendon	UBERON:0000043	89.53	gold quality
ventricular zone	UBERON:0003053	89.19	gold quality
amniotic fluid	UBERON:0000173	88.36	gold quality
tendon of biceps brachii	UBERON:0008188	88.17	gold quality
caput epididymis	UBERON:0004358	88.11	gold quality
fallopian tube	UBERON:0003889	87.98	gold quality
corpus callosum	UBERON:0002336	87.80	gold quality
corpus epididymis	UBERON:0004359	87.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.38	gold quality
left coronary artery	UBERON:0001626	87.30	gold quality
adipose tissue	UBERON:0001013	87.15	gold quality
nasal cavity mucosa	UBERON:0001826	87.07	gold quality
tibia	UBERON:0000979	87.04	gold quality
epithelium of nasopharynx	UBERON:0001951	86.86	gold quality
connective tissue	UBERON:0002384	86.79	gold quality
islet of Langerhans	UBERON:0000006	86.65	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	55.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF4

miRNA regulators (miRDB)

21 targeting FAIM, 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-4776-3P	100.00	68.73	1340
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-6838-3P	98.40	65.88	559
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-4771	97.43	67.69	596

Literature-anchored findings (GeneRIF, showing 12)

• Human keratinocytes were transfected with either Flip, Faim, or Lifeguard (LFG). Our results suggest that heterotopic expression of antiapoptotic proteins can induce the resistance of keratinocytes to a major mechanism of rejection. (PMID:17912957)
• Expression of the long form of Fas apoptotic inhibitory molecule (FAIML) results in the protection of neurons from the cytotoxic actions of death ligands. (PMID:17942717)
• FAIM acts to specifically enhance CD40 signaling for NF-kappaB activation, IRF-4 expression, and BCL-6 down-regulation in vitro, but has no effect on its own (PMID:19592656)
• FAIM (1-90) was crystallized and diffracted to a resolution of 2.5 A; the crystal belonged to space group P3(1), with unit-cell parameters a=b=58.02, c=71.11 A, alpha=beta=90, gamma=120 degrees. (PMID:20693673)
• FAIM modulates IGF-1-induced Akt activation and IRF4 expression and has a role in multiple myeloma cell survival (PMID:23138182)
• Data indicate that FAIM is a novel regulator of insulin signalling and plays an essential role in energy homoeostasis. (PMID:26866272)
• the anti-apoptotic effect of SRT1720 was mitigated by FAIM knockdown with a small interfering RNA-targeted FAIM. These results indicated that pretreatment with SRT1720 improves survival of aged hMSCs, and enhances their therapeutic efficacy for rat myocardial infarction (MI). (PMID:28383554)
• subcellular fractionation experiments revealed that, in contrast to FAIM-S and FAIM-L, FAIM-S_2a and FAIM-L_2a are able to localize to the nucleus, where they may have additional functions. In summary, here we report on two novel FAIM isoforms that may have relevant roles in the physiology and pathology of the nervous system (PMID:28981531)
• PACAP ameliorates hepatic metabolism and inflammation through up-regulating FAIM in obesity. (PMID:31270932)
• FAIM-S functions as a negative regulator of NF-kappaB pathway and blocks cell cycle progression in NSCLC cells. (PMID:33249986)
• FAIM regulates autophagy through glutaminolysis in lung adenocarcinoma. (PMID:34720024)
• Small Heat Shock Proteins Collaborate with FAIM to Prevent Accumulation of Misfolded Protein Aggregates. (PMID:36233145)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	faima	ENSDARG00000005828
danio_rerio	faimb	ENSDARG00000020814
mus_musculus	Faim	ENSMUSG00000032463
mus_musculus	Faiml	ENSMUSG00000096316
rattus_norvegicus	Faim	ENSRNOG00000030069
rattus_norvegicus	Faiml	ENSRNOG00000048802
drosophila_melanogaster	CG10257	FBGN0033985
caenorhabditis_elegans		WBGENE00016633

Protein

Protein identifiers

Fas apoptotic inhibitory molecule 1 — Q9NVQ4 (reviewed: Q9NVQ4)

All UniProt accessions (2): Q9NVQ4, C9JDZ2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as an inducible effector molecule that mediates Fas resistance produced by surface Ig engagement in B cells.

Subcellular location. Cytoplasm.

Similarity. Belongs to the FAIM1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NVQ4-1	1, FAIM-S	yes
Q9NVQ4-2	2
Q9NVQ4-3	3, FAIM-L

RefSeq proteins (4): NP_001028202, NP_001028203, NP_001028204, NP_060617 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010695	FAIM1	Family
IPR038513	FAIM1_dom_sf	Homologous_superfamily

Pfam: PF06905

UniProt features (31 total): strand 18, turn 4, splice variant 2, sequence variant 2, sequence conflict 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3MX7	X-RAY DIFFRACTION	1.76
2KW1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVQ4-F1	93.86	0.88

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: 128 (showing top): MODULE_255, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_317, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, ROSS_LEUKEMIA_WITH_MLL_FUSIONS, GOBP_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_VIA_DEATH_DOMAIN_RECEPTORS, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_NEGATIVE_REGULATION_OF_APOPTOTIC_SIGNALING_PATHWAY, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP

GO Biological Process (4): apoptotic process (GO:0006915), negative regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902042), regulation of signal transduction (GO:0009966), negative regulation of apoptotic process (GO:0043066)

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

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1
negative regulation of extrinsic apoptotic signaling pathway	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAIM	FAIM2	Q9BWQ8	491
FAIM	PDCD2	Q16342	402
FAIM	NFKBIA	P25963	371
FAIM	PKM	P14618	371
FAIM	ZGRF1	Q86YA3	356
FAIM	SYF2	O95926	355
FAIM	TMSB10	P13472	353
FAIM	CLASP1	Q7Z460	353
FAIM	CFLAR	O15519	353
FAIM	TRIT1	Q9H3H1	353
FAIM	RPL27A	P46776	353
FAIM	UBXN2A	P68543	352
FAIM	AMY1B	P04745	352
FAIM	AMY2A	P04746	352
FAIM	AMY2B	P19961	352

IntAct

17 interactions, top by confidence:

A	B	Type	Score
FAIM	SPRY2	psi-mi:“MI:0915”(physical association)	0.560
KLHDC2	PFDN1	psi-mi:“MI:0914”(association)	0.530
FAIM	WDR47	psi-mi:“MI:0914”(association)	0.500
FAIM	WDR47	psi-mi:“MI:0915”(physical association)	0.500
FAIM	H1-1	psi-mi:“MI:0915”(physical association)	0.400
FAIM	H2BC12L	psi-mi:“MI:0915”(physical association)	0.400
FAIM	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
FAIM	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
B3GALT5	TTI1	psi-mi:“MI:0914”(association)	0.350
TNFRSF1B	MAP3K7	psi-mi:“MI:0914”(association)	0.350
SYS1	COX6B1	psi-mi:“MI:0914”(association)	0.350
DNAJC27	METAP2	psi-mi:“MI:0914”(association)	0.350
RSPH1	FAIM	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): FAIM (Two-hybrid), FAIM (Affinity Capture-MS), FAIM (Two-hybrid), FAIM (Affinity Capture-MS), FAIM (Two-hybrid), FAIM (Two-hybrid), FAIM (Two-hybrid), FAIM (Two-hybrid), FAIM (Two-hybrid), ZNF16 (Two-hybrid), INCA1 (Two-hybrid), FAIM (Proximity Label-MS), FAIM (Proximity Label-MS), FAIM (Proximity Label-MS), FAIM (Proximity Label-MS)

ESM2 similar proteins: A2AQW0, A6H7H7, A8K855, D4ABP9, E9Q4Z2, F1QR43, F4IDS7, F4JVN6, G4LTX4, O00763, O18756, O35099, O94923, P19447, P49135, Q0E908, Q0IIF6, Q0J6P7, Q0VEJ0, Q1RMT1, Q24498, Q4G005, Q5BJI9, Q5IH13, Q5IH14, Q5RA62, Q5RCP7, Q6YXW6, Q7K556, Q7ZYD9, Q8BPM2, Q8CI95, Q8K4M9, Q8R5H8, Q8VZM1, Q91XL9, Q940Y1, Q94E75, Q99683, Q9BXB4

Diamond homologs: Q0IIF6, Q8R5H8, Q9NVQ4, Q9WUD8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1096 predictions. Top by Δscore:

Variant	Effect	Δscore
3:138619664:T:TA	acceptor_gain	1.0000
3:138619667:T:A	acceptor_gain	1.0000
3:138619670:A:AG	acceptor_gain	1.0000
3:138619690:T:TA	acceptor_gain	1.0000
3:138619691:G:A	acceptor_gain	1.0000
3:138621405:A:AG	acceptor_gain	1.0000
3:138621406:G:GG	acceptor_gain	1.0000
3:138621406:GC:G	acceptor_gain	1.0000
3:138621406:GCC:G	acceptor_gain	1.0000
3:138621406:GCCC:G	acceptor_gain	1.0000
3:138621406:GCCCT:G	acceptor_gain	1.0000
3:138621512:C:T	donor_gain	1.0000
3:138621520:T:TA	donor_gain	1.0000
3:138621521:A:AA	donor_gain	1.0000
3:138621538:AGGTA:A	donor_loss	1.0000
3:138621541:T:A	donor_loss	1.0000
3:138622184:GTAG:G	acceptor_loss	1.0000
3:138622185:TA:T	acceptor_loss	1.0000
3:138622186:A:AC	acceptor_loss	1.0000
3:138622186:A:AG	acceptor_gain	1.0000
3:138622187:G:GG	acceptor_gain	1.0000
3:138622187:GGAA:G	acceptor_gain	1.0000
3:138622337:G:GT	donor_gain	1.0000
3:138629101:TTACA:T	acceptor_loss	1.0000
3:138629102:TACAG:T	acceptor_loss	1.0000
3:138629103:ACAGA:A	acceptor_loss	1.0000
3:138629104:CAGA:C	acceptor_loss	1.0000
3:138629105:A:AG	acceptor_gain	1.0000
3:138629105:AGA:A	acceptor_loss	1.0000
3:138629106:G:GA	acceptor_gain	1.0000

AlphaMissense

1355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:138621450:T:A	W8R	0.996
3:138621450:T:C	W8R	0.996
3:138632936:T:C	F133L	0.994
3:138632938:T:A	F133L	0.994
3:138632938:T:G	F133L	0.994
3:138622374:T:A	W100R	0.992
3:138622374:T:C	W100R	0.992
3:138622270:T:A	I65K	0.990
3:138621452:G:C	W8C	0.989
3:138621452:G:T	W8C	0.989
3:138621490:T:C	F21S	0.988
3:138621517:G:C	R30P	0.988
3:138621511:G:A	G28D	0.986
3:138622212:T:C	F46L	0.986
3:138622214:C:A	F46L	0.986
3:138622214:C:G	F46L	0.986
3:138622219:T:C	L48S	0.985
3:138622270:T:G	I65R	0.985
3:138622376:G:C	W100C	0.985
3:138622376:G:T	W100C	0.985
3:138621523:T:A	V32E	0.982
3:138633039:T:A	L167H	0.982
3:138621497:T:A	H23Q	0.980
3:138621497:T:G	H23Q	0.980
3:138621511:G:T	G28V	0.980
3:138622213:T:C	F46S	0.980
3:138622305:T:C	Y77H	0.980
3:138633039:T:C	L167P	0.980
3:138621451:G:C	W8S	0.979
3:138621484:T:A	I19N	0.978

dbSNP variants (sampled 300 via entrez): RS1000257199 (3:138625545 A>G), RS1000271818 (3:138609826 C>A,G), RS1000411654 (3:138617292 A>T), RS1000451690 (3:138624189 T>C), RS1000586804 (3:138623866 G>A), RS1000841024 (3:138618472 G>C), RS1000909411 (3:138615308 G>A,T), RS1000981001 (3:138616496 T>G), RS1001036951 (3:138629803 G>A), RS1001135845 (3:138610310 A>G), RS1001154423 (3:138628896 A>G), RS1001165179 (3:138610676 G>A), RS1001509747 (3:138633682 G>A,C), RS1001530183 (3:138629641 T>C), RS1001563531 (3:138624700 A>G,T)

Disease associations

OMIM: gene MIM:617535 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_2492	Blood protein levels	8.000000e-07
GCST006661_139	Male-pattern baldness	3.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, decreases expression	7
Phenobarbital	affects expression, decreases expression	2
Tretinoin	decreases expression, increases expression	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
quercitrin	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
motexafin gadolinium	decreases expression, affects cotreatment	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Dexamethasone	increases expression	1
Diazinon	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

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