SACM1L

protein-coding

SAC1 like phosphatidylinositide phosphatase, the group of Phosphoinositide phosphatases

Gene summary

This gene encodes an integral membrane protein, which is localized to the endoplasmic reticulum, and functions as a phosphoinositide phosphatase that hydrolyzes phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, and phosphatidylinositol 3,5-bisphosphate. Deletion of this gene in mouse results in preimplantation lethality. Other studies suggest that this gene is also involved in the organization of golgi membranes and mitotic spindles. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame, downstream translation termination codon via a stop codon readthrough mechanism.[provided by RefSeq, Dec 2017]

MANE transcript

NM_014016.5

Inheritance

—

ClinVar variants

U:63B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr3:45,689,056-45,745,412

External References & Databases

Ensembl (ENSG00000211456)

Transcript & Mutation Effects

hg38 • Region Span ~56.4 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 SACM1L variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014016.5. 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			2
missense			58 clinvar	2 clinvar		60
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	63	2	0	65

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014016.5	RefSeq	NP_054735.3	20	MANE Select
ENST00000389061.10	Ensembl	ENSP00000373713.4	20	MANE Select
NM_001319071.2	RefSeq	NP_001306000.1	20	Standard
NM_001319072.2	RefSeq	NP_001306001.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Metabolism of lipids
3-phosphoinositide degradation
Metabolism

Biological Process

phosphatidylinositol biosynthetic process
phosphatidylinositol dephosphorylation

Molecular Function

phosphatidylinositol-3-phosphatase activity
protein binding
phosphatase activity
phosphatidylinositol bisphosphate phosphatase activity
phosphatidylinositol phosphate 4-phosphatase activity

Cellular Component

Golgi membrane
endoplasmic reticulum
endoplasmic reticulum membrane
Golgi apparatus
integral component of endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389061
Coding exons: 20
Length: 56369
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125746
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.99	209	307	0.680	0.0000153	3871
Missense (PolyPhen)		38	85.631	0.44377		1030
Synonymous	0.747	96	106	0.908	0.00000563	1042
Loss of Function	4.60	8	39.0	0.205	0.00000206	456

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000063	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000071	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphoinositide phosphatase that hydrolyzes phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 4-phosphate (PtdIns(4)P) (PubMed:24209621). Has low activity towards PtdIns(3,5)P2 (By similarity). {ECO:0000250|UniProtKB:Q9ES21, ECO:0000269|PubMed:24209621}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.601
RVIS EVS: -0.42
RVIS percentile EVS: 25.56

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.811

Gene Damage Prediction

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