SPTSSA

protein-coding

serine palmitoyltransferase small subunit A

Gene summary

Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the first committed and rate-limiting step in sphingolipid biosynthesis. SSSPTA is a small SPT subunit that stimulates SPT activity and confers acyl-CoA preference to the SPT catalytic heterodimer of SPTLC1 (MIM 605712) and either SPTLC2 (MIM 605713) or SPTLC3 (MIM 611120) (Han et al., 2009 [PubMed 19416851]).[supplied by OMIM, Nov 2010]

Previous symbols:

C14orf147

MANE transcript

NM_138288.4

Inheritance

AD, AR

ClinVar variants

P:2U:13

Top phenotype

Spastic paraplegia 90A, autosomal dominant; Spastic paraplegia 90B, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr14:34,432,788-34,462,240

External References & Databases

Ensembl (ENSG00000165389)

Transcript & Mutation Effects

hg38 • Region Span ~29.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spastic paraplegia 90A, autosomal dominantMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0957308

Submitter: G2P

spastic paraplegia 90A, autosomal dominantLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957308

Submitter: G2P

spastic paraplegia 90B, autosomal recessiveLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0957309

Submitter: Labcorp Genetics (formerly Invitae)

spastic paraplegia 90B, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0957309

Submitter: PanelApp Australia

spastic paraplegia 90A, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957308

Submitter: Labcorp Genetics (formerly Invitae)

spastic paraplegia 90A, autosomal dominantMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0957308

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spastic paraplegia 90A, autosomal dominant; Spastic paraplegia 90B, autosomal recessive AD/AR

Manifestation: Audiologic/Otolaryngologic; Neurologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 36718090

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPTSSA variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 13

Spastic paraplegia 90A, autosomal dominantTotal: 1

Spastic paraplegia 90B, autosomal recessiveTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138288.4. 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						0
missense	1 clinvar		13 clinvar			14
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	2	0	13	0	0	15

Highest pathogenic variant AF is 0.000029741805

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138288.4	RefSeq	NP_612145.2	2	MANE Select
ENST00000298130.5	Ensembl	ENSP00000298130.4	2	MANE Select
ENST00001119163.1	Ensembl	ENSP00000788968.1	2	Standard
ENST00001136251.1	Ensembl	ENSP00000805250.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
ceramide <i>de novo</i> biosynthesis
Sphingolipid de novo biosynthesis
Sphingolipid metabolism

Biological Process

sphingolipid biosynthetic process
ceramide biosynthetic process

Molecular Function

serine C-palmitoyltransferase activity
protein binding

Cellular Component

endoplasmic reticulum membrane
integral component of membrane
serine C-palmitoyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298130
Coding exons: 2
Length: 29568
Individuals with no LoFs: 102420
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 102421
p: 0.00000488

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.228	36	40.1	0.899	0.00000201	451
Missense (PolyPhen)		4	9.3588	0.42741		122
Synonymous	-0.970	23	17.8	1.29	0.00000101	135
Loss of Function	1.69	0	3.35	0.00	1.44e-7	36

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000011	0.000011	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stimulates the activity of serine palmitoyltransferase (SPT). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2- SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16- CoA as substrates, with a slight preference for C14-CoA. {ECO:0000269|PubMed:19416851}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

RVIS EVS: -0.05
RVIS percentile EVS: 49.39

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): K
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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