ISM2

protein-coding

isthmin 2, the group of Isthmin family

Gene summary

The protein encoded by this gene contains a type 1 thrombospondin domain, which is present in thrombospondin, a number of proteins involved in the complement pathway, as well as in extracellular matrix proteins. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Mar 2009]

Previous symbols:

THSD3

MANE transcript

NM_199296.3

Inheritance

—

ClinVar variants

U:96B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr14:77,474,394-77,498,816

External References & Databases

Ensembl (ENSG00000100593)

Transcript & Mutation Effects

hg38 • Region Span ~24.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ISM2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 102

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_199296.3. 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				4 clinvar		4
missense			95 clinvar	5 clinvar	1 clinvar	101
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	96	9	1	106

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_199296.3	RefSeq	NP_954993.1	7	MANE Select
ENST00000342219.9	Ensembl	ENSP00000341490.4	7	MANE Select
NM_182509.4	RefSeq	NP_872315.2	6	Standard
ENST00000216481.10	Ensembl	ENSP00000216481.6	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342219
Coding exons: 7
Length: 24471
Individuals with no LoFs: 125632
Homozygous LoFs: 0
Heterozygous LoFs: 115
Defined: 125747
p: 0.000457

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.346	307	325	0.946	0.0000189	3660
Missense (PolyPhen)		91	97.922	0.92931		907
Synonymous	-0.320	143	138	1.03	0.00000848	1144
Loss of Function	0.881	19	23.6	0.804	0.00000111	262

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00085	0.00084	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.770
RVIS EVS: 0.34
RVIS percentile EVS: 73.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.115

Gene Damage Prediction

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