IGSF3

protein-coding

immunoglobulin superfamily member 3, the group of V-set domain containing

Gene summary

The protein encoded by this gene is an immunoglobulin-like membrane protein containing several V-type Ig-like domains. A mutation in this gene has been associated with bilateral nasolacrimal duct obstruction (LCDD). [provided by RefSeq, Jun 2016]

MANE transcript

NM_001007237.3

Inheritance

ClinVar variants

P:3U:176B:34

Top phenotype

Lacrimal duct defect

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr1:116,574,399-116,667,755

External References & Databases

Ensembl (ENSG00000143061)

Transcript & Mutation Effects

hg38 • Region Span ~93.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial congenital nasolacrimal duct obstructionSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0007871

Submitter: Orphanet

familial congenital nasolacrimal duct obstructionLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007871

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Lacrimal duct defectAR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Awareness may allow early surgical treatemnt of nasolacrimal duct obstruction/dacryocystocele, which may be beneficial to avoid complications

Refs: 24372406

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IGSF3 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 197

not providedTotal: 16

IGSF3-related disorderTotal: 7

Familial congenital nasolacrimal duct obstructionTotal: 3

Pyloric stenosisTotal: 1

Myoepithelial tumorTotal: 1

Esophageal atresiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001007237.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				16 clinvar	3 clinvar	19
missense			176 clinvar	12 clinvar	3 clinvar	191
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)						0
Total	1	2	176	28	6	213

Highest pathogenic variant AF is 0.00021167038

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001007237.3	RefSeq	NP_001007238.1	10	MANE Select
ENST00000369486.8	Ensembl	ENSP00000358498.4	10	MANE Select
NM_001542.4	RefSeq	NP_001533.2	11	Standard
ENST00000318837.6	Ensembl	ENSP00000321184.6	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

lacrimal gland development

Molecular Function

molecular_function

Cellular Component

cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369483
Coding exons: 11
Length: 93345
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125748
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.77	631	769	0.820	0.0000497	7927
Missense (PolyPhen)		150	231.49	0.64798		2404
Synonymous	-1.23	353	325	1.09	0.0000222	2451
Loss of Function	5.34	13	56.1	0.232	0.00000319	530

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00034	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00022	0.00020	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.502
RVIS EVS: -1.34
RVIS percentile EVS: 4.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.353

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium