MFSD8

major facilitator superfamily domain containing 8

Basic information

Region (hg38): 4:127917799-127966034

Previous symbols: [ "CLN7" ]

Links

ENSG00000164073 ∙ NCBI:256471 ∙ OMIM:611124 ∙ HGNC:28486 ∙ Uniprot:Q8NHS3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronal ceroid lipofuscinosis 7 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 7 (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 7 (Supportive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 7 (Strong), mode of inheritance: AR
• macular dystrophy with central cone involvement (Strong), mode of inheritance: AR
• neuronal ceroid lipofuscinosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ceroid lipofuscinosis, neuronal, 7	AR	Neurologic	The condition can include severe sequelae, including seizures, and use of a patient-specific antisense oligonucleotide has been reported as benefiting clinical findings, including related to seizure control	Biochemical; Neurologic; Ophthalmologic	15074367; 15965709; 17564970; 19277732; 19201763; 18850119; 22612257; 31597037

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MFSD8 gene.

• Neuronal ceroid lipofuscinosis 7 (60 variants)
• not provided (12 variants)
• Macular dystrophy with central cone involvement (4 variants)
• Late-infantile neuronal ceroid lipofuscinosis (3 variants)
• Macular dystrophy with central cone involvement;Neuronal ceroid lipofuscinosis 7 (2 variants)
• Inborn genetic diseases (2 variants)
• Microcephaly 5, primary, autosomal recessive (1 variants)
• Neuronal ceroid lipofuscinosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MFSD8 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			5	201	1	207
missense	1	8	275	2	1	287
nonsense	20	5	3			28
start loss		4				4
frameshift	33	8	2			43
inframe indel						0
splice donor/acceptor (+/-2bp)	10	32	3			45
splice region			15	39	4	58
non coding			39	137	36	212
Total	64	57	327	340	38

Highest pathogenic variant AF is 0.00000658

Variants in MFSD8

This is a list of pathogenic ClinVar variants found in the MFSD8 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-127917941-A-G		Neuronal ceroid lipofuscinosis 7	Likely benign (Jan 12, 2018)
4-127917947-G-A		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918017-A-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918038-T-C		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918165-T-C		Neuronal ceroid lipofuscinosis 7	Benign (Jan 13, 2018)
4-127918166-G-A		Neuronal ceroid lipofuscinosis 7	Benign (Jan 13, 2018)
4-127918225-C-T		Neuronal ceroid lipofuscinosis 7	Benign (Jan 12, 2018)
4-127918243-AG-A		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
4-127918261-G-C		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 13, 2018)
4-127918316-C-T		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918321-C-T		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918336-C-T		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 13, 2018)
4-127918360-C-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 13, 2018)
4-127918416-T-C		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 13, 2018)
4-127918484-T-C		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 13, 2018)
4-127918526-A-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 13, 2018)
4-127918609-G-A		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918620-A-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918624-T-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Apr 28, 2017)
4-127918661-C-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127918712-A-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Mar 23, 2018)
4-127918836-C-A		Neuronal ceroid lipofuscinosis 7	Benign (Jan 12, 2018)
4-127918921-C-G		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 13, 2018)
4-127918950-T-C		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)
4-127919027-G-A		Neuronal ceroid lipofuscinosis 7	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MFSD8	protein_coding	protein_coding	ENST00000296468	12	48191

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.54e-12	0.425	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.115	275	280	0.981	0.0000138	3351
Missense in Polyphen		83	104.1	0.79727		1189
Synonymous	-0.0179	97	96.8	1.00	0.00000485	1025
Loss of Function	1.27	22	29.5	0.747	0.00000154	331

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000474	0.000474
Ashkenazi Jewish	0.00	0.00
East Asian	0.000490	0.000489
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000490	0.000489
South Asian	0.000131	0.000131
Other	0.000656	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be a carrier that transport small solutes by using chemiosmotic ion gradients. {ECO:0000305}.
• Disease: DISEASE: Macular dystrophy with central cone involvement (CCMD) [MIM:616170]: An ocular disease characterized by decreased visual acuity, slight pigmentary changes and color vision abnormalities, becoming apparent in the third to sixth decade of life. Fundus anomalies are variable and include bull's eye maculopathy, severe atrophy of central fovea, relatively spared fovea with surrounding atrophic ring, central retinal pigment epithelium and/or choroid changes, pale or atrophic peripapillary area, pale optic disk, relatively spared periphery, and slightly or moderately attenuated vessels. {ECO:0000269|PubMed:25227500}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.467
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.46

Haploinsufficiency Scores

• pHI: 0.0942
• hipred: N
• hipred_score: 0.237
• ghis: 0.515

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0863

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mfsd8
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton 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); muscle phenotype; cellular phenotype

Gene ontology

• Biological process: lysosome organization;regulation of autophagy;neuron development;transmembrane transport
• Cellular component: nucleoplasm;lysosomal membrane;integral component of membrane;intracellular membrane-bounded organelle