SLC27A4

protein-coding

solute carrier family 27 member 4, the group of Acyl-CoA synthetase family|Solute carrier family 27

Gene summary

This gene encodes a member of a family of fatty acid transport proteins, which are involved in translocation of long-chain fatty acids cross the plasma membrane. This protein is expressed at high levels on the apical side of mature enterocytes in the small intestine, and appears to be the principal fatty acid transporter in enterocytes. Clinical studies suggest this gene as a candidate gene for the insulin resistance syndrome. Mutations in this gene have been associated with ichthyosis prematurity syndrome. [provided by RefSeq, Apr 2010]

MANE transcript

NM_005094.4

Inheritance

ClinVar variants

P:56U:142B:212

Top phenotype

Ichthyosis prematurity syndrome

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr9:128,340,527-128,361,470

External References & Databases

Ensembl (ENSG00000167114)

Transcript & Mutation Effects

hg38 • Region Span ~20.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ichthyosis prematurity syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012089

Submitter: PanelApp Australia

ichthyosis prematurity syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012089

Submitter: Labcorp Genetics (formerly Invitae)

ichthyosis prematurity syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012089

Submitter: Orphanet

ichthyosis prematurity syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012089

Submitter: G2P

ichthyosis prematurity syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012089

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Ichthyosis prematurity syndromeAR

Manifestation: Dermatologic; Obstetric

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The obstetric manifestations involve maternal mid-trimester complications of pregnancy leading to prematurity

Refs: 19631310; 21856041; 22927265

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC27A4 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 402

Inborn genetic diseasesTotal: 114

Ichthyosis prematurity syndromeTotal: 41

not specifiedTotal: 16

SLC27A4-related disorderTotal: 12

Lamellar ichthyosisTotal: 5

Autosomal recessive congenital ichthyosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005094.4. 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			3 clinvar	201 clinvar	3 clinvar	207
missense	4 clinvar	10 clinvar	134 clinvar	8 clinvar		156
nonsense	5 clinvar	7 clinvar				12
start loss	1 clinvar					1
frameshift	10 clinvar	3 clinvar	1 clinvar			14
splice donor/acceptor (+/-2bp)	3 clinvar	13 clinvar	4 clinvar			20
Total	23	33	142	209	3	410

Highest pathogenic variant AF is 0.00015179264

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005094.4	RefSeq	NP_005085.2	12	MANE Select
ENST00000300456.5	Ensembl	ENSP00000300456.3	12	MANE Select
ENST00000372870.5	Ensembl	ENSP00000361961.1	6	Standard
ENST00000372870.6	Ensembl	ENSP00000361961.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin resistance - Homo sapiens (human)
Fat digestion and absorption - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
PPAR signaling pathway
Transport of fatty acids

Biological Process

medium-chain fatty acid transport
long-chain fatty acid metabolic process
lipid metabolic process
response to nutrient
fatty acid transport

Molecular Function

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

Cellular Component

endoplasmic reticulum membrane
plasma membrane
microvillus
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300456
Coding exons: 12
Length: 20825
Individuals with no LoFs: 125670
Homozygous LoFs: 0
Heterozygous LoFs: 78
Defined: 125748
p: 0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.232	400	413	0.968	0.0000299	4142
Missense (PolyPhen)		158	176.13	0.89707		1760
Synonymous	-0.790	190	177	1.08	0.0000124	1347
Loss of Function	2.76	12	27.7	0.433	0.00000138	316

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00063	0.00060	rare
European (Non-Finnish)	0.00045	0.00044	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in translocation of long-chain fatty acids (LFCA) across the plasma membrane. Appears to be the principal fatty acid transporter in small intestinal enterocytes. Plays a role in the formation of the epidermal barrier. Required for fat absorption in early embryogenesis. Has acyl-CoA ligase activity for long-chain and very-long-chain fatty acids (VLCFAs). Indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Prevents light-induced degeneration of rods and cones (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.187

Intolerance Scores

LoFtool: 0.636
RVIS EVS: -1.08
RVIS percentile EVS: 7.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

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