ISYNA1

protein-coding

inositol-3-phosphate synthase 1

Gene summary

This gene encodes an inositol-3-phosphate synthase enzyme. The encoded protein plays a critical role in the myo-inositol biosynthesis pathway by catalyzing the rate-limiting conversion of glucose 6-phosphate to myoinositol 1-phosphate. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 4. [provided by RefSeq, Nov 2011]

MANE transcript

NM_016368.5

Inheritance

—

ClinVar variants

U:76B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr19:18,434,388-18,438,167

External References & Databases

Ensembl (ENSG00000105655)

Transcript & Mutation Effects

hg38 • Region Span ~3.8 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 ISYNA1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016368.5. 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			2 clinvar	4 clinvar	3 clinvar	9
missense			67 clinvar		1 clinvar	68
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	76	4	4	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016368.5	RefSeq	NP_057452.1	10	MANE Select
ENST00000338128.13	Ensembl	ENSP00000337746.7	10	MANE Select
NM_001170938.2	RefSeq	NP_001164409.1	9	Standard
NM_001253389.2	RefSeq	NP_001240318.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Inositol Phosphate Metabolism
Inositol Metabolism
Inositol phosphate metabolism
Metabolism

Biological Process

inositol biosynthetic process
phospholipid biosynthetic process
inositol phosphate metabolic process

Molecular Function

inositol-3-phosphate synthase activity
protein binding

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338128
Coding exons: 10
Length: 3914
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125745
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.27	288	355	0.811	0.0000231	3549
Missense (PolyPhen)		86	149.92	0.57363		1513
Synonymous	-1.35	192	170	1.13	0.0000128	1168
Loss of Function	2.14	11	21.8	0.506	0.00000112	223

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000069	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.000099	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Key enzyme in myo-inositol biosynthesis pathway that catalyzes the conversion of glucose 6-phosphate to 1-myo-inositol 1-phosphate in a NAD-dependent manner. Rate-limiting enzyme in the synthesis of all inositol-containing compounds. {ECO:0000269|PubMed:15024000}.;

Recessive Scores

pRec: 0.166

Intolerance Scores

LoFtool: 0.115
RVIS EVS: -0.62
RVIS percentile EVS: 17.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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