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 (Definitive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 7 (Strong), 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 7 (Supportive), mode of inheritance: AR
• neuronal ceroid lipofuscinosis 7 (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 (800 variants)
• not_provided (176 variants)
• Late-infantile_neuronal_ceroid_lipofuscinosis (137 variants)
• Inborn_genetic_diseases (98 variants)
• Macular_dystrophy_with_central_cone_involvement (46 variants)
• not_specified (39 variants)
• Retinal_dystrophy (14 variants)
• Neuronal_ceroid_lipofuscinosis (9 variants)
• MFSD8-related_disorder (9 variants)
• Cone-rod_dystrophy (2 variants)
• MF5D8-related_disorder (1 variants)
• Optic_atrophy (1 variants)
• Microcephaly_5,_primary,_autosomal_recessive (1 variants)
• Intellectual_disability (1 variants)
• Retinitis_pigmentosa (1 variants)
• Hereditary_ataxia (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Neuronal_Ceroid-Lipofuscinosis,_Recessive (1 variants)
• Retinal_disorder (1 variants)
• Seizure (1 variants)
• Severe_early-childhood-onset_retinal_dystrophy (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. These statistics are base on transcript: NM_001371596.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	222	1	233
missense	6	24	308	11		349
nonsense	23	14	2			39
start loss		4				4
frameshift	39	11				50
splice donor/acceptor (+/-2bp)	12	38	3			53
Total	80	91	323	233	1

Highest pathogenic variant AF is 0.0000464718

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
		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

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

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