REPS1

RALBP1 associated Eps domain containing 1, the group of EF-hand domain containing

Basic information

Region (hg38): 6:138903492-138988261

Links

ENSG00000135597 ∙ NCBI:85021 ∙ OMIM:614825 ∙ HGNC:15578 ∙ Uniprot:Q96D71 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration with brain iron accumulation 7 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration with brain iron accumulation 7	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	Neurologic	29395073

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the REPS1 gene.

• not provided (128 variants)
• Inborn genetic diseases (19 variants)
• Neurodegeneration with brain iron accumulation 7 (4 variants)
• Neurodegeneration with brain iron accumulation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the REPS1 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				28	5	33
missense	1		67	5	3	76
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	6	4	12
non coding			1	18	2	21
Total	1	0	68	51	10

Highest pathogenic variant AF is 0.000197

Variants in REPS1

This is a list of pathogenic ClinVar variants found in the REPS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-138905135-GA-G			Benign/Likely benign (Feb 01, 2024)
6-138907479-TC-AT			Likely benign (Nov 22, 2023)
6-138907487-T-C			Benign (Oct 24, 2022)
6-138907513-T-C			Likely benign (Jan 08, 2024)
6-138907515-C-T			Uncertain significance (Dec 02, 2021)
6-138907516-G-A			Likely benign (Nov 21, 2022)
6-138907591-C-T			Likely benign (Aug 16, 2022)
6-138907610-T-C			Likely benign (Dec 02, 2021)
6-138907618-G-A			Likely benign (Mar 13, 2023)
6-138908677-G-A		not specified	Uncertain significance (Oct 05, 2023)
6-138908685-T-G			Likely benign (Jan 29, 2024)
6-138908686-G-A			Uncertain significance (Oct 03, 2023)
6-138908689-G-A			Uncertain significance (Apr 12, 2023)
6-138908713-G-A		not specified	Conflicting classifications of pathogenicity (Sep 27, 2022)
6-138908719-T-G			Uncertain significance (Dec 13, 2023)
6-138908729-C-G			Uncertain significance (Jul 25, 2022)
6-138908730-A-G			Likely benign (Dec 02, 2021)
6-138908735-C-T			Benign (Jan 31, 2024)
6-138908777-C-T			Uncertain significance (Nov 01, 2022)
6-138908783-T-C			Uncertain significance (Apr 12, 2022)
6-138908823-G-A			Benign (Jan 22, 2024)
6-138908828-G-T			Likely benign (Oct 17, 2022)
6-138908831-T-C			Likely benign (Dec 02, 2021)
6-138911287-G-A		Neurodegeneration with brain iron accumulation 7 • REPS1-related disorder	Benign/Likely benign (Dec 28, 2023)
6-138911306-T-G		REPS1-related disorder	Benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
REPS1	protein_coding	protein_coding	ENST00000258062	20	84769

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0149	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.70	331	430	0.770	0.0000222	5149
Missense in Polyphen		123	213.81	0.57527		2661
Synonymous	0.827	140	153	0.915	0.00000819	1602
Loss of Function	5.14	7	43.6	0.160	0.00000209	518

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000185	0.000185
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000345	0.0000327
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May coordinate the cellular actions of activated EGF receptors and Ral-GTPases. {ECO:0000250}.
• Disease: DISEASE: Neurodegeneration with brain iron accumulation 7 (NBIA7) [MIM:617916]: A neurodegenerative disorder associated with iron accumulation, primarily in the basal ganglia. Clinical features include speech and motor delay, truncal hypotonia, progressive cerebellar ataxia, and loss of ambulation. NBIA7 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:29395073}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.462
• rvis_EVS: -0.13
• rvis_percentile_EVS: 43.98

Haploinsufficiency Scores

• pHI: 0.282
• hipred: Y
• hipred_score: 0.739
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Reps1

Gene ontology

• Biological process: receptor-mediated endocytosis;membrane organization
• Cellular component: cytosol;plasma membrane;clathrin-coated pit
• Molecular function: calcium ion binding;protein binding;SH3 domain binding