SIRAL2

Summary

SIRAL2 (SIR2 antiphage like 2, HGNC:1313) is a protein-coding gene on chromosome 22q13.31, encoding Protein FAM118A (Q9NWS6).

Enables identical protein binding activity. Predicted to be located in membrane.

Source: NCBI Gene 55007 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_017911

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1313
Approved symbol	SIRAL2
Name	SIR2 antiphage like 2
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	SIRal2, FLJ20635, bK268H5.C22.4
Ensembl gene	ENSG00000100376
Ensembl biotype	protein_coding
Entrez	55007

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 38 protein_coding, 7 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000216214, ENST00000405673, ENST00000424557, ENST00000427777, ENST00000441876, ENST00000452238, ENST00000459849, ENST00000462361, ENST00000476478, ENST00000476754, ENST00000477714, ENST00000479180, ENST00000481447, ENST00000483102, ENST00000487732, ENST00000491671, ENST00000894423, ENST00000894424, ENST00000894425, ENST00000894426, ENST00000894427, ENST00000894428, ENST00000894429, ENST00000915810, ENST00000915811, ENST00000915812, ENST00000915813, ENST00000915814, ENST00000915815, ENST00000915816, ENST00000915817, ENST00000915818, ENST00000915819, ENST00000915820, ENST00000915821, ENST00000915822, ENST00000951640, ENST00000951641, ENST00000951642, ENST00000951643, ENST00000951644, ENST00000951645, ENST00000951646, ENST00000951647, ENST00000951648, ENST00000951649, ENST00000951650, ENST00000951651

RefSeq mRNA: 6 — MANE Select: NM_017911 NM_001104595, NM_001349913, NM_001349914, NM_001349915, NM_001349916, NM_017911

CCDS: CCDS14065

Canonical transcript exons

ENST00000441876 — 9 exons

Exon	Start	End
ENSE00000657067	45327842	45328063
ENSE00001046457	45340386	45341955
ENSE00001556181	45309934	45310183
ENSE00003478739	45322371	45322426
ENSE00003551406	45330603	45330731
ENSE00003557773	45323175	45323427
ENSE00003602411	45336328	45336411
ENSE00003614336	45332425	45332710
ENSE00003655600	45335350	45335382

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 96.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7491 / max 273.5790, expressed in 1741 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192708	5.0964	1564
192711	2.9036	1218
192715	0.6128	74
192707	0.3784	180
192713	0.2341	85
192709	0.1824	55
192710	0.1626	51
192714	0.1122	26
192716	0.0313	16
192712	0.0311	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.31	gold quality
left testis	UBERON:0004533	95.94	gold quality
gall bladder	UBERON:0002110	95.33	gold quality
transverse colon	UBERON:0001157	94.25	gold quality
pituitary gland	UBERON:0000007	93.95	gold quality
left ovary	UBERON:0002119	93.79	gold quality
right ovary	UBERON:0002118	93.76	gold quality
testis	UBERON:0000473	93.72	gold quality
adenohypophysis	UBERON:0002196	93.71	gold quality
right coronary artery	UBERON:0001625	93.55	gold quality
ascending aorta	UBERON:0001496	93.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.40	gold quality
thoracic aorta	UBERON:0001515	93.33	gold quality
gastrocnemius	UBERON:0001388	93.31	gold quality
body of uterus	UBERON:0009853	93.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.14	gold quality
lower esophagus	UBERON:0013473	93.12	gold quality
vagina	UBERON:0000996	93.01	gold quality
right lobe of thyroid gland	UBERON:0001119	92.97	gold quality
muscle of leg	UBERON:0001383	92.86	gold quality
right atrium auricular region	UBERON:0006631	92.82	gold quality
rectum	UBERON:0001052	92.80	gold quality
descending thoracic aorta	UBERON:0002345	92.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.72	gold quality
left lobe of thyroid gland	UBERON:0001120	92.42	gold quality
minor salivary gland	UBERON:0001830	92.22	gold quality
right uterine tube	UBERON:0001302	92.16	gold quality
aorta	UBERON:0000947	91.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting SIRAL2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-802	99.61	67.70	1254

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fam118a	ENSMUSG00000022434
rattus_norvegicus	Fam118a	ENSRNOG00000013764

Paralogs (1): FAM118B (ENSG00000197798)

Protein

Protein identifiers

Protein FAM118A — Q9NWS6 (reviewed: Q9NWS6)

All UniProt accessions (5): Q9NWS6, B0QY26, B0QY27, B0QY28, B0QY29

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the FAM118 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NWS6-1	1	yes
Q9NWS6-2	2

RefSeq proteins (6): NP_001098065, NP_001336842, NP_001336843, NP_001336844, NP_001336845, NP_060381* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038916	FAM118	Family

Pfam: PF13289

UniProt features (8 total): modified residue 2, sequence variant 2, chain 1, transmembrane region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWS6-F1	83.77	0.66

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, 311

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GGGACCA_MIR133A_MIR133B, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, chr22q13, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_UP, GSE13522_CTRL_VS_T_CRUZI_BRAZIL_STRAIN_INF_SKIN_UP, CHAF1B_TARGET_GENES, HOXC6_TARGET_GENES, NAB2_TARGET_GENES, NFKBIA_TARGET_GENES, SALL4_TARGET_GENES, SOX10_TARGET_GENES, ZBTB12_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1145 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SIRAL2	TMEM39B	Q9GZU3	522
SIRAL2	TTC38	Q5R3I4	519
SIRAL2	DNAJC18	Q9H819	506
SIRAL2	LETM2	Q2VYF4	491
SIRAL2	RHBDD3	Q9Y3P4	479
SIRAL2	SPMIP7	A4D263	476
SIRAL2	ERICH1	Q86X53	476
SIRAL2	LAPTM4A	Q15012	466
SIRAL2	NRF1	Q16656	464
SIRAL2	REEP6	Q96HR9	460
SIRAL2	GPAT2	Q6NUI2	439
SIRAL2	TRMU	O75648	434
SIRAL2	BBS9	P78514	429
SIRAL2	PLD6	Q8N2A8	424
SIRAL2	RAPGEFL1	Q9UHV5	424

IntAct

72 interactions, top by confidence:

A	B	Type	Score
WDR4	FAM118A	psi-mi:“MI:0915”(physical association)	0.780
FAM118A	WDR4	psi-mi:“MI:0915”(physical association)	0.780
FAM118A	ATOX1	psi-mi:“MI:0915”(physical association)	0.720
AIDA	FAM118A	psi-mi:“MI:0915”(physical association)	0.720
FAM118A	FAM118B	psi-mi:“MI:0915”(physical association)	0.720
FAM118A	AIDA	psi-mi:“MI:0915”(physical association)	0.720
ATOX1	FAM118A	psi-mi:“MI:0915”(physical association)	0.720
FAM118B	FAM118A	psi-mi:“MI:0915”(physical association)	0.720
MOB3C	FAM118A	psi-mi:“MI:0915”(physical association)	0.670
LNX1	FAM118A	psi-mi:“MI:0915”(physical association)	0.670
FAM118A	MOB3C	psi-mi:“MI:0915”(physical association)	0.670
FAM118A	FAM118A	psi-mi:“MI:0915”(physical association)	0.670
FAM118A	LNX1	psi-mi:“MI:0915”(physical association)	0.670
TNFSF13B	IPO8	psi-mi:“MI:0914”(association)	0.640
SDCBP	FAM118A	psi-mi:“MI:0915”(physical association)	0.560
FAM118A	GLRX3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (30): FAM118A (Two-hybrid), FAM118A (Two-hybrid), FAM118A (Two-hybrid), FAM118A (Two-hybrid), FAM118A (Two-hybrid), MOB1A (Two-hybrid), AIDA (Two-hybrid), FAM118B (Two-hybrid), LNX1 (Two-hybrid), MOB3C (Two-hybrid), FAM118A (Affinity Capture-MS), FAM118A (Two-hybrid), FAM118A (Affinity Capture-MS), FAM118A (Two-hybrid), FAM118A (Two-hybrid)

ESM2 similar proteins: A2QRA0, A2RSY6, A4QNR3, A5D7S3, A6NHR9, O13559, P03271, P03272, P03273, P09507, P0CX14, P0CX15, P0CX20, P0CX21, P0CX22, P12540, P38899, P40105, P40434, P40889, P48752, P53819, P78746, P87552, Q03099, Q07888, Q08995, Q0WL81, Q3E7X8, Q3E7Y5, Q496Z9, Q5R5T0, Q65945, Q69ZX6, Q6P5D8, Q7Z2T5, Q7Z494, Q8GW10, Q8NG08, Q8R5F7

Diamond homologs: Q4QQT2, Q4R836, Q5E977, Q8C569, Q91YN1, Q9BPY3, Q9NWS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2567 predictions. Top by Δscore:

Variant	Effect	Δscore
22:45319552:GCC:G	donor_gain	1.0000
22:45323169:A:AG	acceptor_gain	1.0000
22:45323170:A:G	acceptor_gain	1.0000
22:45323171:G:GG	acceptor_gain	1.0000
22:45323171:GTA:G	acceptor_gain	1.0000
22:45323174:GAAA:G	acceptor_gain	1.0000
22:45323365:A:T	donor_gain	1.0000
22:45323415:G:GT	donor_gain	1.0000
22:45323428:G:GG	donor_gain	1.0000
22:45327841:GCGC:G	acceptor_gain	1.0000
22:45330585:T:A	acceptor_gain	1.0000
22:45330600:TAGGT:T	acceptor_loss	1.0000
22:45330602:G:T	acceptor_loss	1.0000
22:45332424:GGAA:G	acceptor_gain	1.0000
22:45336406:A:G	donor_gain	1.0000
22:45322370:GAA:G	acceptor_gain	0.9900
22:45323171:GT:G	acceptor_gain	0.9900
22:45323171:GTAGA:G	acceptor_gain	0.9900
22:45323172:TAGA:T	acceptor_loss	0.9900
22:45323173:A:AG	acceptor_gain	0.9900
22:45323174:G:GT	acceptor_gain	0.9900
22:45323174:GA:G	acceptor_gain	0.9900
22:45323174:GAA:G	acceptor_gain	0.9900
22:45323424:ACCT:A	donor_gain	0.9900
22:45323425:CCT:C	donor_gain	0.9900
22:45323426:CT:C	donor_gain	0.9900
22:45323427:TG:T	donor_loss	0.9900
22:45323428:G:A	donor_loss	0.9900
22:45323429:T:TG	donor_loss	0.9900
22:45323430:AAGT:A	donor_loss	0.9900

AlphaMissense

2358 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:45323283:G:C	W52C	0.999
22:45323283:G:T	W52C	0.999
22:45323230:G:T	G35W	0.998
22:45323231:G:A	G35E	0.998
22:45323242:A:C	S39R	0.998
22:45323244:C:A	S39R	0.998
22:45323244:C:G	S39R	0.998
22:45323281:T:A	W52R	0.998
22:45323281:T:C	W52R	0.998
22:45323408:T:C	L94P	0.998
22:45327985:C:A	N148K	0.998
22:45327985:C:G	N148K	0.998
22:45327990:A:C	D150A	0.998
22:45327990:A:T	D150V	0.998
22:45330645:C:G	H189D	0.998
22:45330651:C:G	H191D	0.998
22:45323225:T:A	V33D	0.997
22:45323399:C:A	A91D	0.997
22:45327975:T:C	L145P	0.997
22:45327978:C:T	T146I	0.997
22:45327989:G:C	D150H	0.997
22:45330640:T:A	V187D	0.997
22:45332465:T:C	F231S	0.997
22:45332492:A:T	D240V	0.997
22:45323231:G:T	G35V	0.996
22:45327893:T:C	F118L	0.996
22:45327895:T:A	F118L	0.996
22:45327895:T:G	F118L	0.996
22:45330612:T:A	W178R	0.996
22:45330612:T:C	W178R	0.996

dbSNP variants (sampled 300 via entrez): RS1000021236 (22:45311209 T>G), RS1000064132 (22:45319701 T>C), RS1000070813 (22:45325641 G>A), RS1000155834 (22:45316794 C>G), RS1000206340 (22:45316545 G>A,C), RS1000215982 (22:45313906 T>C), RS1000415743 (22:45327601 C>T), RS1000456531 (22:45311361 C>A,G,T), RS1000490235 (22:45308497 T>C,G), RS1000512720 (22:45315267 C>G,T), RS1000546781 (22:45314998 C>T), RS1000709309 (22:45322704 A>G), RS1000709786 (22:45309950 C>G,T), RS1000720377 (22:45326150 G>A), RS1000775814 (22:45309006 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST005537_68	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	6.000000e-10
GCST005723_1	Peanut allergy (maternal genetic effects)	4.000000e-06
GCST006979_830	Heel bone mineral density	1.000000e-19
GCST007576_101	Chronotype	6.000000e-10
GCST008295_38	Number of decayed, missing and filled tooth surfaces or use of dentures	1.000000e-11
GCST008306_21	Dentures	1.000000e-09
GCST008362_74	Birth weight	1.000000e-08
GCST008839_269	Height	3.000000e-14
GCST010726_77	Periventricular white matter hyperintensities	2.000000e-06
GCST012203_3	Colon cancer	3.000000e-08
GCST012205_7	Distal colorectal cancer	2.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005939	parental genotype effect measurement
EFO:0007017	peanut allergy measurement
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0010078	dentures
EFO:0004344	birth weight
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	2
Valproic Acid	increases expression	2
FR900359	increases phosphorylation	1
terbufos	increases methylation	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methotrexate	decreases expression	1
Parathion	increases methylation	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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