ELOVL4

ELOVL fatty acid elongase 4

Basic information

Region (hg38): 6:79914813-79947553

Previous symbols: [ "STGD2", "STGD3", "SCA34" ]

Links

ENSG00000118402 ∙ NCBI:6785 ∙ OMIM:605512 ∙ HGNC:14415 ∙ Uniprot:Q9GZR5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (Definitive), mode of inheritance: AR
• spinocerebellar ataxia type 34 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 34 (Moderate), mode of inheritance: AD
• congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (Strong), mode of inheritance: AR
• Stargardt disease (Supportive), mode of inheritance: AD
• spinocerebellar ataxia type 34 (Supportive), mode of inheritance: AD
• congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (Supportive), mode of inheritance: AR
• Stargardt disease 3 (Definitive), mode of inheritance: AD
• congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (Strong), mode of inheritance: AR
• spinocerebellar ataxia type 34 (Strong), mode of inheritance: AD
• Stargardt disease 3 (Strong), mode of inheritance: AD
• Stargardt disease 3 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, spastic quadriplegia, and mental retardation; Spinocerebellar ataxia 34; Startgardt disease 3	AD/AR	General	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	Biochemical; Dermatologic; Neurologic; Ophthalmologic	10634627; 11726641; 11138005; 15557430; 22100072; 24566826

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ELOVL4 gene.

• not provided (214 variants)
• Stargardt disease 3 (65 variants)
• Inborn genetic diseases (7 variants)
• not specified (6 variants)
• Spinocerebellar ataxia type 34 (6 variants)
• Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (5 variants)
• Stargardt Disease, Dominant (3 variants)
• ELOVL4-Related Disorders (2 variants)
• Retinal dystrophy (2 variants)
• Stargardt disease 3;Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome;Spinocerebellar ataxia type 34 (1 variants)
• Spinocerebellar ataxia type 34;Stargardt disease 3;Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (1 variants)
• ELOVL4-related ataxia (1 variants)
• Spastic ataxia (1 variants)
• Stargardt disease 3;Spinocerebellar ataxia type 34;Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ELOVL4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	41		43
missense	2	2	90	2	2	98
nonsense	2	3	1			6
start loss						0
frameshift	7	1	1			9
inframe indel						0
splice donor/acceptor (+/-2bp)		3				3
splice region		1	6	5	1	13
non coding			36	24	33	93
Total	11	9	130	67	35

Variants in ELOVL4

This is a list of pathogenic ClinVar variants found in the ELOVL4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-79914939-A-C		Stargardt disease 3	Benign (Jan 12, 2018)
6-79915040-T-C		Stargardt disease 3	Uncertain significance (Jan 12, 2018)
6-79915054-ATATGT-A		Stargardt Disease, Dominant	Uncertain significance (Jun 14, 2016)
6-79915057-T-C		Stargardt disease 3	Benign (Jan 12, 2018)
6-79915097-C-T		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915102-T-C		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915185-T-C		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915367-A-C		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915415-A-G		Stargardt disease 3	Uncertain significance (Jan 12, 2018)
6-79915542-A-C		Stargardt disease 3	Benign (Jan 13, 2018)
6-79915558-T-C		Stargardt disease 3	Benign (Jan 13, 2018)
6-79915560-C-T		Stargardt disease 3	Uncertain significance (Jan 12, 2018)
6-79915570-T-C		Stargardt disease 3	Uncertain significance (Jan 12, 2018)
6-79915588-T-C		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915609-T-C		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915658-A-G		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915703-A-G		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79915805-A-G		Stargardt disease 3	Uncertain significance (Jan 12, 2018)
6-79915812-CAT-C		Stargardt Disease, Dominant	Benign (Jun 14, 2016)
6-79915941-A-G		Stargardt disease 3	Benign (Jan 13, 2018)
6-79915999-C-T		Stargardt disease 3	Benign (Jan 13, 2018)
6-79916002-C-A		Stargardt disease 3	Uncertain significance (Jan 13, 2018)
6-79916099-G-A		Stargardt disease 3	Benign (Jan 13, 2018)
6-79916231-A-T		Stargardt disease 3	Benign (Jan 13, 2018)
6-79916235-T-A		Stargardt disease 3	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ELOVL4	protein_coding	protein_coding	ENST00000369816	6	32769

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.832	0.168	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	126	169	0.744	0.00000819	2068
Missense in Polyphen		29	60.249	0.48134		735
Synonymous	-0.284	60	57.3	1.05	0.00000265	566
Loss of Function	3.41	3	19.1	0.157	9.98e-7	198

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the first and rate-limiting reaction of the four that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. Condensing enzyme that specifically elongates C24:0 and C26:0 acyl-CoAs. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May play a critical role in early brain and skin development. {ECO:0000255|HAMAP-Rule:MF_03204, ECO:0000269|PubMed:20937905}.
• Disease: DISEASE: Stargardt disease 3 (STGD3) [MIM:600110]: A common hereditary macular degeneration. It is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. {ECO:0000269|PubMed:11138005, ECO:0000269|PubMed:11581213}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ichthyosis, spastic quadriplegia, and mental retardation (ISQMR) [MIM:614457]: A severe autosomal recessive disorder characterized by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. {ECO:0000269|PubMed:22100072}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 34 (SCA34) [MIM:133190]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA34 is an autosomal dominant form characterized by the association of progressive cerebellar ataxia with erythrokeratodermia variabilis. {ECO:0000269|PubMed:24566826}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fatty acid elongation - Homo sapiens (human);Alpha Linolenic Acid and Linoleic Acid Metabolism;Ectoderm Differentiation;Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Fatty acid metabolism;Synthesis of very long-chain fatty acyl-CoAs (Consensus)

Recessive Scores

• pRec: 0.0997

Intolerance Scores

• loftool: 0.545
• rvis_EVS: 0.39
• rvis_percentile_EVS: 76.05

Haploinsufficiency Scores

• pHI: 0.694
• hipred: Y
• hipred_score: 0.738
• ghis: 0.445

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.144

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Elovl4
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype

Gene ontology

• Biological process: fatty acid biosynthetic process;unsaturated fatty acid biosynthetic process;detection of visible light;fatty acid elongation, saturated fatty acid;sphingolipid biosynthetic process;fatty acid elongation, monounsaturated fatty acid;fatty acid elongation, polyunsaturated fatty acid;long-chain fatty-acyl-CoA biosynthetic process;very long-chain fatty acid biosynthetic process
• Cellular component: endoplasmic reticulum;integral component of endoplasmic reticulum membrane
• Molecular function: protein binding;G protein-coupled photoreceptor activity;fatty acid elongase activity;3-oxo-arachidoyl-CoA synthase activity;3-oxo-cerotoyl-CoA synthase activity;3-oxo-lignoceronyl-CoA synthase activity;very-long-chain 3-ketoacyl-CoA synthase activity