IGSF23

Summary

IGSF23 (immunoglobulin superfamily member 23, HGNC:40040) is a protein-coding gene on chromosome 19q13.31, encoding Immunoglobulin superfamily member 23 (A1L1A6). May be involved in osteoclast differentiation.

This gene encodes a protein that has one immunoglobulin (Ig) domain and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways.

Source: NCBI Gene 147710 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001205280

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40040
Approved symbol	IGSF23
Name	immunoglobulin superfamily member 23
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000216588
Ensembl biotype	protein_coding
Entrez	147710

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000402988, ENST00000428245, ENST00000441389, ENST00000592507, ENST00000911252, ENST00000911253

RefSeq mRNA: 1 — MANE Select: NM_001205280 NM_001205280

CCDS: CCDS54277

Canonical transcript exons

ENST00000402988 — 5 exons

Exon	Start	End
ENSE00001552388	44623707	44623972
ENSE00001555123	44627420	44627573
ENSE00001559870	44635401	44635465
ENSE00001561643	44636419	44636781
ENSE00001562716	44613563	44613770

Expression profiles

Bgee: expression breadth ubiquitous, 114 present calls, max score 90.66.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0676 / max 14.2137, expressed in 25 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176262	0.0293	13
176261	0.0241	15
176263	0.0142	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.66	gold quality
right lobe of liver	UBERON:0001114	87.49	gold quality
duodenum	UBERON:0002114	84.21	gold quality
liver	UBERON:0002107	84.12	gold quality
small intestine	UBERON:0002108	66.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	66.44	gold quality
mucosa of transverse colon	UBERON:0004991	60.99	gold quality
body of pancreas	UBERON:0001150	60.69	gold quality
pancreas	UBERON:0001264	56.35	gold quality
right testis	UBERON:0004534	54.53	gold quality
left testis	UBERON:0004533	53.00	gold quality
testis	UBERON:0000473	52.83	gold quality
heart left ventricle	UBERON:0002084	51.63	gold quality
adult mammalian kidney	UBERON:0000082	51.29	gold quality
colonic epithelium	UBERON:0000397	51.23	silver quality
right uterine tube	UBERON:0001302	50.62	gold quality
kidney	UBERON:0002113	50.27	gold quality
cortex of kidney	UBERON:0001225	49.78	gold quality
right coronary artery	UBERON:0001625	49.45	gold quality
rectum	UBERON:0001052	48.98	gold quality
intestine	UBERON:0000160	48.35	gold quality
islet of Langerhans	UBERON:0000006	48.19	gold quality
transverse colon	UBERON:0001157	47.57	gold quality
placenta	UBERON:0001987	47.56	gold quality
blood	UBERON:0000178	46.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	46.43	gold quality
sural nerve	UBERON:0015488	46.28	gold quality
stromal cell of endometrium	CL:0002255	45.71	gold quality
lower esophagus mucosa	UBERON:0035834	45.05	silver quality
leukocyte	CL:0000738	44.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting IGSF23, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-642B-5P	96.37	67.26	745
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-2114-3P	95.45	66.11	579

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Igsf23	ENSMUSG00000040498
rattus_norvegicus	Igsf23	ENSRNOG00000024630

Protein

Protein identifiers

Immunoglobulin superfamily member 23 — A1L1A6 (reviewed: A1L1A6)

All UniProt accessions (4): A1L1A6, H0Y6S3, H0Y773, K7EL25

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in osteoclast differentiation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in bone and small intestine. Highly expressed in osteoclasts, and low expressed in osteoblasts and peripheral blood mononuclear cells (PBMCs).

RefSeq proteins (1): NP_001192209* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

UniProt features (7 total): chain 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1L1A6-F1	78.55	0.48

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_CELL_CELL_ADHESION, GOBP_OSTEOCLAST_DIFFERENTIATION, MIKKELSEN_ES_ICP_WITH_H3K4ME3, FEVR_CTNNB1_TARGETS_UP, GSE14415_NATURAL_TREG_VS_FOXP3_KO_NATURAL_TREG_DN, ZNF37A_TARGET_GENES, ZNF664_TARGET_GENES, ZSCAN2_TARGET_GENES, MIR4311, MIR659_3P, GSE13229_MATURE_VS_INTMATURE_NKCELL_UP, MIR3934_5P

GO Biological Process (1): osteoclast differentiation (GO:0030316)

GO Molecular Function (0):

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
myeloid leukocyte differentiation	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGSF23	LCN15	Q6UWW0	474
IGSF23	C1orf226	A1L170	473
IGSF23	PLEKHM1	Q9Y4G2	456
IGSF23	OSTM1	Q86WC4	451
IGSF23	TM4SF20	Q53R12	450
IGSF23	CLCN7	P51798	445
IGSF23	MTRNR2L10	P0CJ77	445
IGSF23	TCIRG1	Q13488	443
IGSF23	FCRLA	Q7L513	433
IGSF23	GRIK5	Q16478	427
IGSF23	ADTRP	Q96IZ2	426
IGSF23	EPS8L3	Q8TE67	424
IGSF23	FABP6	P51161	419
IGSF23	FCRL5	Q96RD9	418
IGSF23	SLC10A2	Q12908	405

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0JNM1, A1L1A6, A6QNY1, A6QQC6, B0CLX4, B2RTN2, B8JI67, D3YX43, O02733, O88324, P01881, P01883, P12342, P21995, P26898, P86176, Q01151, Q0VCB1, Q0VFL4, Q2YDG7, Q3U0X8, Q5RCS3, Q5UKY4, Q6AXW8, Q6PCB8, Q7TMJ8, Q7TQM3, Q7TSN7, Q8BJN4, Q8IW00, Q8N7X8, Q8R526, Q8TBE3, Q8TDX9, Q8VCP9, Q8VD31, Q91V87, Q91ZV2, Q91ZV3, Q96FE7

Diamond homologs: A1L1A6, B2RTN2, D3ZQE1, G4SLH0, Q2WEN9, Q9UQ72

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1027 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44623968:GCCAA:G	donor_gain	1.0000
19:44623973:G:GG	donor_gain	1.0000
19:44623700:C:G	acceptor_gain	0.9900
19:44623970:CAAGT:C	donor_loss	0.9900
19:44623972:AGT:A	donor_loss	0.9900
19:44623974:TGA:T	donor_loss	0.9900
19:44623975:GAGTC:G	donor_loss	0.9900
19:44623976:AGTC:A	donor_loss	0.9900
19:44627418:A:AG	acceptor_gain	0.9900
19:44627419:G:GG	acceptor_gain	0.9900
19:44613769:GT:G	donor_gain	0.9800
19:44623701:A:AG	acceptor_gain	0.9800
19:44623702:G:GG	acceptor_gain	0.9800
19:44623702:GACA:G	acceptor_gain	0.9800
19:44635461:AAGAG:A	donor_loss	0.9800
19:44635462:AGAGG:A	donor_loss	0.9800
19:44635464:AGG:A	donor_loss	0.9800
19:44635465:GGTA:G	donor_loss	0.9800
19:44635466:G:C	donor_loss	0.9800
19:44635467:T:A	donor_loss	0.9800
19:44635476:G:GT	donor_gain	0.9800
19:44636417:AGAT:A	acceptor_gain	0.9800
19:44636417:AGATG:A	acceptor_gain	0.9800
19:44636418:GATG:G	acceptor_gain	0.9800
19:44636418:GATGG:G	acceptor_gain	0.9800
19:44613771:G:GG	donor_gain	0.9700
19:44623699:A:AG	acceptor_gain	0.9700
19:44623702:GAC:G	acceptor_gain	0.9700
19:44634646:GCCAC:G	donor_gain	0.9700
19:44635394:A:AG	acceptor_gain	0.9700

AlphaMissense

1238 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44623830:G:C	W83C	0.981
19:44623830:G:T	W83C	0.981
19:44623828:T:A	W83R	0.978
19:44623828:T:C	W83R	0.978
19:44623762:A:C	S61R	0.977
19:44623764:T:A	S61R	0.977
19:44623764:T:G	S61R	0.977
19:44623919:C:A	A113D	0.976
19:44623732:T:C	F51L	0.975
19:44623734:C:A	F51L	0.975
19:44623734:C:G	F51L	0.975
19:44623883:T:C	L101S	0.970
19:44623787:T:C	L69P	0.969
19:44623914:C:G	C111W	0.966
19:44623874:T:C	I98T	0.963
19:44623912:T:A	C111S	0.962
19:44623913:G:C	C111S	0.962
19:44623792:T:A	W71R	0.960
19:44623792:T:C	W71R	0.960
19:44623906:T:G	Y109D	0.960
19:44623926:C:A	N115K	0.960
19:44623926:C:G	N115K	0.960
19:44623918:G:C	A113P	0.959
19:44623781:T:A	V67E	0.957
19:44623829:G:C	W83S	0.955
19:44623961:T:G	I127S	0.955
19:44623961:T:A	I127N	0.954
19:44623868:T:C	L96P	0.949
19:44623961:T:C	I127T	0.945
19:44623912:T:C	C111R	0.944

dbSNP variants (sampled 300 via entrez): RS1000030203 (19:44627976 G>C,T), RS1000040120 (19:44627654 C>T), RS1000140092 (19:44620620 G>T), RS1000245840 (19:44615055 C>G,T), RS1000253227 (19:44633475 G>A), RS1000285993 (19:44621069 C>G,T), RS1000618033 (19:44620842 CA>C,CAA), RS1000668501 (19:44616959 C>A), RS1000855298 (19:44632136 T>C), RS1000891552 (19:44622802 C>A,G), RS1001037473 (19:44625975 C>G), RS1001163604 (19:44627254 G>A), RS1001352710 (19:44633605 A>G), RS1001365957 (19:44621641 A>G), RS1001484233 (19:44635170 C>T)

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

15 associations (top):

Study	Trait	p-value
GCST003815_9	Late-onset Alzheimer’s disease	3.000000e-06
GCST005950_15	Body mass index x sex x age interaction (4df test)	2.000000e-10
GCST005951_56	Body mass index	1.000000e-06
GCST005952_8	Body mass index (age>50)	9.000000e-12
GCST005954_4	Body mass index x age interaction	2.000000e-07
GCST007320_50	Alzheimer’s disease or family history of Alzheimer’s disease	2.000000e-11
GCST007320_84	Alzheimer’s disease or family history of Alzheimer’s disease	1.000000e-09
GCST007827_17	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-12
GCST007827_19	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-11
GCST007827_5	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-74
GCST007827_6	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-54
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-36
GCST009597_264	Multiple sclerosis	1.000000e-09
GCST010204_45	Low density lipoprotein cholesterol levels	9.000000e-295
GCST010243_210	Apolipoprotein B levels	0.000000e+00

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:1001870	late-onset Alzheimers disease
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
Benzo(a)pyrene	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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