FAF1

Summary

FAF1 (Fas associated factor 1, HGNC:3578) is a protein-coding gene on chromosome 1p32.3, encoding FAS-associated factor 1 (Q9UNN5). Ubiquitin-binding protein.

Interaction of Fas ligand (TNFSF6) with the FAS antigen (TNFRSF6) mediates programmed cell death, also called apoptosis, in a number of organ systems. The protein encoded by this gene binds to FAS antigen and can initiate apoptosis or enhance apoptosis initiated through FAS antigen. Initiation of apoptosis by the protein encoded by this gene requires a ubiquitin-like domain but not the FAS-binding domain.

Source: NCBI Gene 11124 — RefSeq curated summary.

At a glance

• GWAS associations: 58
• Clinical variants (ClinVar): 97 total
• Druggable target: yes
• MANE Select transcript: NM_007051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3578
Approved symbol	FAF1
Name	Fas associated factor 1
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-03, hFAF1, HFAF1s, UBXD12, UBXN3A
Ensembl gene	ENSG00000185104
Ensembl biotype	protein_coding
OMIM	604460
Entrez	11124

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000396153, ENST00000472808, ENST00000487898, ENST00000494400, ENST00000888953, ENST00000888956, ENST00000888958, ENST00000888960, ENST00000888962, ENST00000888964, ENST00000952057, ENST00000952058, ENST00000952059, ENST00000952060, ENST00000952061

RefSeq mRNA: 1 — MANE Select: NM_007051 NM_007051

CCDS: CCDS554

Canonical transcript exons

ENST00000396153 — 19 exons

Exon	Start	End
ENSE00001293798	50535369	50535457
ENSE00001298822	50491721	50491801
ENSE00001302601	50490588	50490665
ENSE00001326285	50655442	50655528
ENSE00001326948	50475464	50475679
ENSE00001656216	50959767	50960267
ENSE00001661954	50705786	50705891
ENSE00001819739	50437028	50441523
ENSE00003515494	50788000	50788205
ENSE00003537777	50584685	50584811
ENSE00003550173	50857929	50857997
ENSE00003580374	50738863	50738954
ENSE00003596808	50596121	50596216
ENSE00003615461	50744684	50744775
ENSE00003643422	50539592	50539728
ENSE00003656635	50801631	50801677
ENSE00003662565	50567077	50567231
ENSE00003664682	50582618	50582699
ENSE00003684656	50583652	50583715

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9850 / max 270.4276, expressed in 1821 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12276	22.4004	1816
12277	3.8208	1398
12275	1.5122	814
12274	0.2516	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	97.08	gold quality
muscle of leg	UBERON:0001383	96.93	gold quality
left testis	UBERON:0004533	96.60	gold quality
right testis	UBERON:0004534	96.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.22	gold quality
muscle organ	UBERON:0001630	95.89	gold quality
ganglionic eminence	UBERON:0004023	95.37	gold quality
gluteal muscle	UBERON:0002000	95.25	gold quality
triceps brachii	UBERON:0001509	95.24	gold quality
testis	UBERON:0000473	95.20	gold quality
ventricular zone	UBERON:0003053	95.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.95	gold quality
body of pancreas	UBERON:0001150	94.56	gold quality
deltoid	UBERON:0001476	94.52	gold quality
popliteal artery	UBERON:0002250	94.47	gold quality
tibial artery	UBERON:0007610	94.47	gold quality
biceps brachii	UBERON:0001507	94.45	gold quality
calcaneal tendon	UBERON:0003701	94.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.32	gold quality
skin of leg	UBERON:0001511	94.30	gold quality
rectum	UBERON:0001052	94.13	gold quality
cortical plate	UBERON:0005343	94.13	gold quality
heart left ventricle	UBERON:0002084	94.09	gold quality
islet of Langerhans	UBERON:0000006	94.02	gold quality
cardiac ventricle	UBERON:0002082	94.00	gold quality
skeletal muscle tissue	UBERON:0001134	93.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.87	gold quality
skin of abdomen	UBERON:0001416	93.86	gold quality
tendon	UBERON:0000043	93.68	gold quality
right atrium auricular region	UBERON:0006631	93.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF1, NFKB1, NR3C2, RELA

miRNA regulators (miRDB)

23 targeting FAF1, 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-450B-5P	99.92	71.48	3175
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-595	98.25	67.44	699
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-562	97.66	65.63	698

Literature-anchored findings (GeneRIF, showing 40)

• FAF1 is a member of Fas-DISC acting upstream of caspase-8 (PMID:12702723)
• phosphorylation by protein kinase CK2 influencing transport into nucleus (PMID:12832043)
• FAS-associated factor 1 is specifically reduced in human gastric carcinomas (PMID:12963981)
• a novel function of FAF1: NF-kappaB activity suppressor by cytoplasmic retention of NF-kappaB p65 via physical interaction. (PMID:14600157)
• hFAF1 prevents cells from recovery after stress by binding to and inhibiting the chaperone activity of Hsp70 (PMID:15596450)
• hFAF1 may serve as a scaffolding protein that regulates protein degradation in the ubiquitin-proteasome pathway. (PMID:15743842)
• FAF1 functions as a negative regulator of an NF-kappaB signal pathway that involves PYPAF1 and ASC. (PMID:17046979)
• FAF1 robustly suppresses NF-kappaB activation through the inhibition of IKK activation in combination with previously reported cytoplasmic retention of NF-kappaB p65 (PMID:17684021)
• Fas expression was reduced and caspase-10 activity was decreased in both patients (PMID:17999750)
• Changes in FAF1 expression were specific to PD-related alpha-synuclein pathology and nigral cell loss. These studies, together with previous genetic linkage studies, highlight the potential significance of FAF1 in pathogenesis of idiopathic PD. (PMID:18573343)
• analysis of the negative feedback regulation of Aurora-A via phosphorylation of Fas-associated factor-1 (PMID:18790738)
• Determined the crystal structure of the ubiquitin-associated domain of human FAF1 (hFAF1-UBA) and examined its interaction with ubiquitin and ubiquitin-like proteins using nuclear magnetic resonance. (PMID:19722279)
• the p97/VCP N domain was crystallized in complex with the FAF1 UBX domain. X-ray data were collected to 2.60 A resolution and the crystals belonged to space group C222(1), with unit-cell parameters a = 58.24, b = 72.81, c = 132.93 A. (PMID:20057067)
• report FAF1 UBX domain crystallization and X-ray data collection. X-ray data were collected to 3.00 A resolution and the crystals belonged to space group F4(1)32, with unit-cell parameters a = b = c = 176.40 A. (PMID:20124726)
• Data show that miR-24 regulates apoptosis by targeting FAF1 in cancer cells. (PMID:20195546)
• Mutations in FAF1 is associated with cleft palate and is necessary for lower jaw development in zebrafish. (PMID:21295280)
• the crystal structure of human FAF1 UBX domain at 2.9A resolution is reported. (PMID:21414298)
• FAF1 and UBXD7 only bind to p97-UFD1/NPL4, but not free p97, thus demonstrating for the first time a hierarchy in p97-cofactor interactions (PMID:21645854)
• In transgenic mice in which FAF1 is expressed in immature olfactory sensory neurons (OSNs), FAF1 not only misroutes OSN axons to deep layers of the olfactory bulb but also disrupts the glomerular layer (PMID:21849551)
• The authors report the first in vitro confirmed non-homotypic interaction between NLRP12 pyrin domain and the pro-apoptotic protein Fas-associated factor 1 (FAF-1), which links the innate immune system to apoptotic signaling. (PMID:21978668)
• Wild-type p97/VCP ND1 in complex with FAF1 UBX crystallized into very thin sheet-shaped crystals which turned out to be of poor diffraction quality (PMID:22102026)
• Fas-associated factor 1 is a scaffold protein that promotes beta-transducin repeat-containing protein (beta-TrCP)-mediated beta-catenin ubiquitination and degradation. (PMID:22730322)
• hFAF1 inhibits tumor formation by increasing the degradation of Hsp70 mediated via its UBA domain. (PMID:22876279)
• Data indicate that Npl4-Ufd1 heterodimer is required for VCP-FAF1 interaction. (PMID:23293021)
• long-chain unsaturated fatty acids also induced polymerization of Fas-associated factor 1 (FAF1), the only other mammalian protein that contains a UAS domain homologous to that of Ubxd8 (PMID:23720822)
• Report a novel role for FAF1 in regulating CD40-induced NFkappaB activation via a negative feedback loop. (PMID:24810049)
• The repertoire of VAPB interactors is more diverse than previously anticipated and link VAPB to the function of ATPase complexes such as p97/FAF1 and ASNA1/transmembrane-domain recognition complex. (PMID:24885147)
• FAF1 plays a novel role in negatively regulating virus-induced IFN-beta production and the antiviral response by inhibiting the translocation of active, phosphorylated IRF3 from the cytosol to the nucleus (PMID:26811330)
• Progression of the DNA replication fork is coordinated by FAF1. FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC48-dependent turnover and disassembly of DNA replication factor complexes. (PMID:26842564)
• confirmation of the association between rs17106184 (FAF1) and Type 2 Diabetes in a northern Han Chinese population (PMID:27589775)
• These data demonstrate the presence of an FAF1-PARP1 axis that is involved in oxidative stress-induced necrosis and in the pathology of Parkinson’s disease. (PMID:27662363)
• Helicobacter pylori, a risk factor for gastric cancer, down-regulated FAF1 expression via NF-kappaB signaling in gastric carcinoma cells, promoting tumor growth. (PMID:28030825)
• Knockdown of FAF1 suppressed Sanguinarine (SNG)-induced inhibition of cell proliferation, invasion, and migration and induction of cell cycle arrest and apoptosis in NSCLC cells. SNG also inhibited implanted tumor growth and increased FAF1 expression in tumors in vivo. (PMID:28296008)
• FAF1 physically interacts with XIAP. FAF1 attenuates XIAP-mediated NF-kappaB activation. (PMID:28414080)
• Data show that activated proto-oncogene protein Akt (AKT) directly phosphorylates Fas associated factor 1 (FAF1) reduces FAF1 at the plasma membrane and results in an increase in TGF-beta type II receptor (TbetaRII) at the cell surface. (PMID:28443643)
• FAF1 was vital in the proliferation of NP cells by modulating the Erk signaling pathway, which suggests that FAF1 may be a novel marker in the early diagnosis of Intervertebral disc degeneration. (PMID:29257270)
• These findings establish FAF1 as a modulator of MAVS and uncover mechanisms that regulate FAF1 to insure timely activation of antiviral defense. (PMID:30472208)
• C18H17NO6 and Scutellarin in the study. In molecular level, the mRNA and protein expression of Fas-associated factor 1 (FAF1) expression in U251 and LN229 were upregulated by C18H17NO6 and its combination with Scutellarin, especially the protein expression. (PMID:30915356)
• the mechanisms of FAF1/SIM-mediated MR transrepression involve inhibition of MR N/C interactions and promotion of MR polyubiquitination and degradation. (PMID:30935967)
• Germline Mutations in FAF1 Are Associated With Hereditary Colorectal Cancer. (PMID:32179092)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	faf1	ENSDARG00000022418
mus_musculus	Faf1	ENSMUSG00000010517
rattus_norvegicus	Faf1	ENSRNOG00000008523
drosophila_melanogaster	casp	FBGN0034068
caenorhabditis_elegans		WBGENE00006718
caenorhabditis_elegans		WBGENE00018586

Paralogs (4): UBXN8 (ENSG00000104691), FAF2 (ENSG00000113194), UBXN10 (ENSG00000162543), UBXN7 (ENSG00000163960)

Protein

Protein identifiers

FAS-associated factor 1 — Q9UNN5 (reviewed: Q9UNN5)

Alternative names: UBX domain-containing protein 12, UBX domain-containing protein 3A

All UniProt accessions (2): B3KT28, Q9UNN5

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-binding protein. Required for the progression of DNA replication forks by targeting DNA replication licensing factor CDT1 for degradation. Potentiates but cannot initiate FAS-induced apoptosis.

Subunit / interactions. Interacts with CDT1 and ATPase VCP/p97. Interacts (via UBA domain) with FAS (via death domain). Interacts (via UBA domain) with NLRP12 (via DAPIN/PYRIN domain).

Subcellular location. Nucleus.

Tissue specificity. Most abundant in testis, slightly less abundant in skeletal muscle and heart, followed by prostate, thymus, ovary, small intestine, and colon. Not detected in the peripheral blood leukocytes.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UNN5-1	Long	yes
Q9UNN5-2	Short, hFAF1(s)

RefSeq proteins (1): NP_008982* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001012	UBX_dom	Domain
IPR006577	UAS	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033043	FAF1-like_UBX	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR044541	FAF1_UBA	Domain
IPR049483	FAF1_2-like_UAS	Domain
IPR050730	UBX_domain-protein	Family

Pfam: PF00789, PF14555, PF21021

UniProt features (48 total): strand 16, helix 15, turn 5, sequence conflict 3, modified residue 3, domain 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
7FGN	X-RAY DIFFRACTION	1.2
3QX1	X-RAY DIFFRACTION	1.6
3E21	X-RAY DIFFRACTION	1.73
3QQ8	X-RAY DIFFRACTION	2
3QWZ	X-RAY DIFFRACTION	2
3QC8	X-RAY DIFFRACTION	2.2
7FGM	X-RAY DIFFRACTION	2.2
3QCA	X-RAY DIFFRACTION	2.9
3R3M	X-RAY DIFFRACTION	3
8KG2	X-RAY DIFFRACTION	3.1
9YW2	ELECTRON MICROSCOPY	3.27
11TA	ELECTRON MICROSCOPY	3.58
11VE	ELECTRON MICROSCOPY	3.85
1H8C	SOLUTION NMR
2DZM	SOLUTION NMR
2EC4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNN5-F1	77.82	0.25

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 (3): 320, 580, 582

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 241 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_DNA_REPLICATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_255, SP3_Q3, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, AREB6_03, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, SP1_Q2_01, EFC_Q6

GO Biological Process (11): apoptotic process (GO:0006915), regulation of cell adhesion (GO:0030155), Fas signaling pathway (GO:0036337), ERAD pathway (GO:0036503), regulation of protein catabolic process (GO:0042176), positive regulation of apoptotic process (GO:0043065), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of protein catabolic process (GO:0045732), positive regulation of DNA replication (GO:0045740), positive regulation of extrinsic apoptotic signaling pathway via death domain receptors (GO:1902043)

GO Molecular Function (8): protein kinase regulator activity (GO:0019887), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), heat shock protein binding (GO:0031072), ubiquitin protein ligase binding (GO:0031625), ubiquitin binding (GO:0043130), NF-kappaB binding (GO:0051059), protein binding (GO:0005515)

GO Cellular Component (14): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), CD95 death-inducing signaling complex (GO:0031265), perinuclear theca (GO:0033011), VCP-NPL4-UFD1 AAA ATPase complex (GO:0034098), perinuclear region of cytoplasm (GO:0048471), ooplasm (GO:1990917), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	4
proteasomal protein catabolic process	2
protein catabolic process	2
protein binding	2
intracellular membrane-bounded organelle	2
endomembrane system	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell adhesion	1
regulation of cellular process	1
cell surface receptor signaling pathway	1
response to endoplasmic reticulum stress	1
response to chemical	1
regulation of catabolic process	1
regulation of protein metabolic process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
positive regulation of catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
DNA replication	1
regulation of DNA replication	1
positive regulation of DNA metabolic process	1
extrinsic apoptotic signaling pathway via death domain receptors	1
regulation of extrinsic apoptotic signaling pathway via death domain receptors	1
positive regulation of extrinsic apoptotic signaling pathway	1
protein kinase activity	1
kinase regulator activity	1
protein kinase binding	1
kinase binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-like protein binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1

Protein interactions and networks

STRING

1583 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAF1	UFD1	Q92890	935
FAF1	VCP	P55072	903
FAF1	FCF1	Q9Y324	847
FAF1	CASP8	Q14790	847
FAF1	FADD	Q13158	839
FAF1	DNTTIP2	Q5QJE6	834
FAF1	NPLOC4	Q8TAT6	802
FAF1	FAS	P25445	768
FAF1	UBXN1	Q04323	741
FAF1	NLRP12	P59046	706
FAF1	FASLG	P48023	664
FAF1	UBXN6	Q9BZV1	589
FAF1	UBXN4	Q92575	575
FAF1	CDKN2C	P42773	574
FAF1	UBXN10	Q96LJ8	562

IntAct

94 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
FAF1	VCP	psi-mi:“MI:0915”(physical association)	0.640
FAF1	VCP	psi-mi:“MI:0914”(association)	0.640
CHCHD10	CLPX	psi-mi:“MI:0914”(association)	0.640
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
YTHDF3	FAF1	psi-mi:“MI:0915”(physical association)	0.560
GRN	FAF1	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	FAF1	psi-mi:“MI:0915”(physical association)	0.560
TCEAL1	CHEK1	psi-mi:“MI:0914”(association)	0.530
BHLHA15	RPLP0	psi-mi:“MI:0914”(association)	0.530
BHLHA15	YBX3	psi-mi:“MI:0914”(association)	0.530
HSPA2	DNAJC13	psi-mi:“MI:0914”(association)	0.530
FAF1	CSNK2B	psi-mi:“MI:0915”(physical association)	0.370
ANXA1	FAF1	psi-mi:“MI:0915”(physical association)	0.370
FAF1	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
FAF1	CDC73	psi-mi:“MI:0915”(physical association)	0.370
FAF1	CDKN1A	psi-mi:“MI:0915”(physical association)	0.370
FAF1	DNAJB11	psi-mi:“MI:0915”(physical association)	0.370
FAF1	HSD17B10	psi-mi:“MI:0915”(physical association)	0.370
FAF1	IGF2	psi-mi:“MI:0915”(physical association)	0.370
FAF1	ITGB1BP1	psi-mi:“MI:0915”(physical association)	0.370
SKIL	FAF1	psi-mi:“MI:0915”(physical association)	0.370
NR1H2	FAF1	psi-mi:“MI:0915”(physical association)	0.370
FAF1	NR4A1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (520): FAF1 (Affinity Capture-Western), FAF1 (Reconstituted Complex), FAF1 (Two-hybrid), UBC (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), UBC (Co-purification), FAF1 (Affinity Capture-MS), FAF1 (Affinity Capture-MS), FAF1 (Co-fractionation), FAF1 (Co-fractionation), FAF1 (Co-fractionation), FAF1 (Affinity Capture-MS), FAF1 (Reconstituted Complex), CDT1 (Affinity Capture-Western), VCP (Affinity Capture-Western)

ESM2 similar proteins: A0JPP7, E9Q4Z2, F1N2W9, F1QDI9, O12940, O35815, O60784, O70593, O88746, O88978, O88984, O95453, P54252, P54731, P58797, P69341, Q0VGM9, Q1RMR5, Q28BP9, Q2HJD0, Q2T9Z1, Q32LM2, Q3TDN2, Q5BK32, Q5R752, Q5RC51, Q5RJZ1, Q68FJ8, Q6AZH6, Q6GQ69, Q6H1L8, Q6R005, Q6TH22, Q7ZU92, Q7ZYA7, Q80W98, Q8BJU0, Q8CFK2, Q8UUU2, Q8VD33

Diamond homologs: O00124, P54731, Q2TBH5, Q924K2, Q9QZ49, Q9UNN5, O14048, O94888, P0DKI4, P0DKI5, Q55BU7, Q5REY7, Q6P5G6, Q94HV8, Q94JZ8, Q9M0N1, F4JPR7, Q4V3D3, Q06682, P34631, Q28BP9, Q2HJD0, Q3TDN2, Q5BK32, Q96CS3, Q9C5G7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
AURKA	“down-regulates activity”	FAF1	phosphorylation
IKBKE	“down-regulates quantity by destabilization”	FAF1	phosphorylation
FAF1	“down-regulates activity”	MAVS	binding
CSNK2A1	“down-regulates activity”	FAF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 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.

GO biological processes:

GO term	Partners	Fold	FDR
macroautophagy	5	12.8×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

5203 predictions. Top by Δscore:

Variant	Effect	Δscore
1:50475462:A:AC	donor_gain	1.0000
1:50475463:C:CC	donor_gain	1.0000
1:50475463:CGT:C	donor_gain	1.0000
1:50475463:CGTCT:C	donor_gain	1.0000
1:50475500:AT:A	donor_gain	1.0000
1:50475500:ATC:A	donor_gain	1.0000
1:50475677:GGCCT:G	acceptor_loss	1.0000
1:50475679:CCTAG:C	acceptor_loss	1.0000
1:50475680:C:CC	acceptor_gain	1.0000
1:50490585:CACCT:C	donor_loss	1.0000
1:50490586:A:AT	donor_loss	1.0000
1:50490661:TCCCT:T	acceptor_gain	1.0000
1:50490662:CCCT:C	acceptor_gain	1.0000
1:50490662:CCCTC:C	acceptor_gain	1.0000
1:50490663:CCT:C	acceptor_gain	1.0000
1:50490663:CCTC:C	acceptor_gain	1.0000
1:50490664:CT:C	acceptor_gain	1.0000
1:50490664:CTC:C	acceptor_gain	1.0000
1:50490665:TC:T	acceptor_loss	1.0000
1:50490665:TCT:T	acceptor_gain	1.0000
1:50490666:C:CA	acceptor_loss	1.0000
1:50490666:C:CC	acceptor_gain	1.0000
1:50490672:A:AC	acceptor_gain	1.0000
1:50490672:A:C	acceptor_gain	1.0000
1:50491708:TG:T	donor_gain	1.0000
1:50491716:CCTA:C	donor_loss	1.0000
1:50491717:CTAC:C	donor_loss	1.0000
1:50491718:TACC:T	donor_loss	1.0000
1:50491720:C:CA	donor_loss	1.0000
1:50491797:TCATC:T	acceptor_gain	1.0000

AlphaMissense

4291 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:50441462:A:G	L644P	1.000
1:50475470:C:A	R621S	1.000
1:50475470:C:G	R621S	1.000
1:50475471:C:A	R621M	1.000
1:50475471:C:G	R621T	1.000
1:50475475:G:A	P620S	1.000
1:50475476:A:C	F619L	1.000
1:50475476:A:T	F619L	1.000
1:50475478:A:G	F619L	1.000
1:50475564:A:G	F590S	1.000
1:50475570:C:G	R588P	1.000
1:50475597:C:G	R579P	1.000
1:50475603:C:G	R577P	1.000
1:50475679:C:G	A552P	1.000
1:50491726:C:G	A524P	1.000
1:50491732:C:G	D522H	1.000
1:50491735:C:G	A521P	1.000
1:50491740:A:G	L519P	1.000
1:50491740:A:T	L519H	1.000
1:50491744:A:G	S518P	1.000
1:50491752:T:G	Y515S	1.000
1:50491753:A:C	Y515D	1.000
1:50491753:A:G	Y515H	1.000
1:50491753:A:T	Y515N	1.000
1:50491756:C:G	A514P	1.000
1:50491763:T:A	Q511H	1.000
1:50491763:T:G	Q511H	1.000
1:50491764:T:G	Q511P	1.000
1:50491772:C:A	K508N	1.000
1:50491772:C:G	K508N	1.000

dbSNP variants (sampled 300 via entrez): RS1000000107 (1:50515061 C>T), RS1000002240 (1:50546977 C>T), RS1000008341 (1:50440080 A>T), RS1000016992 (1:50767337 C>T), RS1000020786 (1:50636012 G>A,C), RS1000021499 (1:50816901 G>A), RS1000021840 (1:50772014 G>C), RS1000022565 (1:50517853 C>T), RS1000030575 (1:50862383 G>C), RS1000032532 (1:50572491 C>T), RS1000036942 (1:50447699 C>G), RS1000037568 (1:50810637 A>C), RS1000046594 (1:50636933 T>C), RS1000051790 (1:50636350 T>C), RS1000063331 (1:50592025 T>C)

Disease associations

OMIM: gene MIM:604460 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

58 associations (top):

Study	Trait	p-value
GCST000872_3	QRS duration	3.000000e-10
GCST001313_3	Depression and alcohol dependence	4.000000e-06
GCST002352_43	Type 2 diabetes	4.000000e-09
GCST003322_2	Ischemic stroke (large artery atherosclerosis)	7.000000e-09
GCST003400_29	Type 2 diabetes	1.000000e-07
GCST004066_100	Hip circumference	4.000000e-06
GCST004066_59	Hip circumference	3.000000e-09
GCST004067_130	Hip circumference adjusted for BMI	2.000000e-09
GCST004067_18	Hip circumference adjusted for BMI	3.000000e-09
GCST004710_1	Renal cell carcinoma	3.000000e-10
GCST004894_34	Type 2 diabetes	1.000000e-08
GCST004894_91	Type 2 diabetes	6.000000e-07
GCST005306_4	Atrial fibrillation	2.000000e-11
GCST005935_1	Ventricular ectopy or supraventricular ectopy (pleiotropy)	1.000000e-08
GCST005937_4	Ventricular ectopy	3.000000e-06
GCST006661_33	Male-pattern baldness	9.000000e-12
GCST006881_6	Hippocampal tail volume (corrected for total hippocampal volume)	4.000000e-10
GCST007096_152	Pulse pressure	2.000000e-11
GCST007097_164	Pulse pressure	4.000000e-09
GCST007097_165	Pulse pressure	2.000000e-07
GCST007227_12	QRS duration	4.000000e-08
GCST007269_12	Pulse pressure	5.000000e-10
GCST007430_14	Peak expiratory flow	1.000000e-37
GCST007431_106	Lung function (FEV1/FVC)	6.000000e-17
GCST007432_30	FEV1	6.000000e-12
GCST007847_80	Type 2 diabetes	3.000000e-11
GCST007847_99	Type 2 diabetes	3.000000e-09
GCST008062_115	Blood urea nitrogen levels	1.000000e-08
GCST008512_1	Multisite chronic pain	5.000000e-09
GCST009379_27	Type 2 diabetes	2.000000e-10

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0009275	premature cardiac contractions
EFO:0009276	ventricular ectopy
EFO:0009277	supraventricular ectopy
EFO:0005763	pulse pressure measurement
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0010100	multisite chronic pain
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0010556	Left ventricular mass to end-diastolic volume ratio
EFO:0008205	left ventricular structural measurement
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3758063 (SINGLE PROTEIN)

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
Benzo(a)pyrene	affects methylation, decreases expression	6
Aflatoxin B1	affects expression, decreases expression, decreases methylation	4
Valproic Acid	affects expression, decreases methylation, increases expression	3
Cisplatin	decreases expression, increases reaction	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
NMS-873	increases reaction, affects binding	1
methylmercuric chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
chromium hexavalent ion	increases abundance, decreases expression	1
rofecoxib	affects expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
jinfukang	decreases expression, increases reaction	1
Bortezomib	increases expression	1
Fulvestrant	increases methylation	1
Vehicle Emissions	affects expression, increases reaction	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Menthol	decreases expression	1
Mustard Gas	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Urethane	increases expression	1
Fenretinide	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3762496	Binding	Binding affinity to FLAG-tagged FAF1 (unknown origin) expressed in H2O2-treated human SH-SY5Y cells after 12 hrs by immunoblot analysis	Design and synthesis of fluorescent and biotin tagged probes for the study of molecular actions of FAF1 inhibitor. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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