SLC27A5

protein-coding

solute carrier family 27 member 5, the group of Solute carrier family 27|Acyl-CoA synthetase family

Gene summary

The protein encoded by this gene is an isozyme of very long-chain acyl-CoA synthetase (VLCS). It is capable of activating very long-chain fatty-acids containing 24- and 26-carbons. It is expressed in liver and associated with endoplasmic reticulum but not with peroxisomes. Its primary role is in fatty acid elongation or complex lipid synthesis rather than in degradation. This gene has a mouse ortholog. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012254.3

Inheritance

—

ClinVar variants

U:220B:78

Top phenotype

SLC27A5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr19:58,479,512-58,512,413

External References & Databases

Ensembl (ENSG00000083807)

Transcript & Mutation Effects

hg38 • Region Span ~32.9 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 SLC27A5 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 196

not specifiedTotal: 128

SLC27A5-related disorderTotal: 126

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012254.3. 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			9 clinvar	51 clinvar	4 clinvar	64
missense			196 clinvar	23 clinvar		219
nonsense			3 clinvar			3
start loss			1 clinvar			1
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	220	74	4	298

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012254.3	RefSeq	NP_036386.1	10	MANE Select
ENST00000263093.7	Ensembl	ENSP00000263093.2	10	MANE Select
NM_001321196.2	RefSeq	NP_001308125.1	10	Standard
ENST00000594786.1	Ensembl	ENSP00000471065.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin resistance - Homo sapiens (human)
Bile secretion - Homo sapiens (human)
Primary bile acid biosynthesis - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
27-Hydroxylase Deficiency

Biological Process

very long-chain fatty acid metabolic process
long-chain fatty acid metabolic process
triglyceride mobilization
bile acid biosynthetic process
bile acid metabolic process

Molecular Function

long-chain fatty acid-CoA ligase activity
long-chain fatty acid transporter activity
ATP binding
fatty acid transmembrane transporter activity
very long-chain fatty acid-CoA ligase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
basal plasma membrane
integral component of endoplasmic reticulum membrane
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263093
Coding exons: 10
Length: 32902
Individuals with no LoFs: 125582
Homozygous LoFs: 0
Heterozygous LoFs: 166
Defined: 125748
p: 0.000660

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.399	401	424	0.946	0.0000258	4322
Missense (PolyPhen)		118	141.68	0.83288		1609
Synonymous	1.43	160	185	0.866	0.0000109	1539
Loss of Function	0.694	24	28.0	0.858	0.00000144	281

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0010	notable
Latino/Admixed American	0.00053	0.00052	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00056	0.00054	rare
Finnish	0.0013	0.0013	notable
European (Non-Finnish)	0.00060	0.00059	rare
South Asian	0.00076	0.00069	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acyl-CoA synthetase involved in bile acid metabolism. Proposed to catalyze the first step in the conjugation of C24 bile acids (choloneates) to glycine and taurine before excretion into bile canaliculi by activating them to their CoA thioesters. Seems to activate secondary bile acids entering the liver from the enterohepatic circulation. In vitro, also activates 3-alpha,7- alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol. {ECO:0000269|PubMed:10749848, ECO:0000269|PubMed:11980911}.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.851
RVIS EVS: 0.29
RVIS percentile EVS: 71.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.810

Gene Damage Prediction

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