PRPH

peripherin, the group of Intermediate filaments Type III

Basic information

Region (hg38): 12:49295147-49298686

Previous symbols: [ "NEF4" ]

Links

ENSG00000135406 ∙ NCBI:5630 ∙ OMIM:170710 ∙ HGNC:9461 ∙ Uniprot:P41219 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis (Limited), mode of inheritance: AD
• amyotrophic lateral sclerosis type 1 (Limited), mode of inheritance: AD

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRPH 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	1	6
missense			47	1	3	51
nonsense		1	1			2
start loss						0
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1		1		2
splice region						0
non coding				1	7	8
Total	0	2	50	8	11

Variants in PRPH

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

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

Position	Type	Phenotype	Significance	ClinVar
12-49295177-G-C			Benign (Sep 29, 2018)
12-49295178-G-C			not provided (-)
12-49295205-G-C		Inborn genetic diseases	Uncertain significance (May 06, 2024)
12-49295216-T-C		Inborn genetic diseases	Uncertain significance (Aug 30, 2022)
12-49295217-C-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
12-49295226-G-A		not specified • Amyotrophic lateral sclerosis type 1	Benign (May 01, 2024)
12-49295263-C-T		PRPH-related disorder	Likely benign (Oct 18, 2021)
12-49295269-A-G			Likely benign (May 18, 2018)
12-49295304-C-G		Inborn genetic diseases	Uncertain significance (Apr 06, 2023)
12-49295346-C-T		Inborn genetic diseases	Uncertain significance (Jun 30, 2023)
12-49295367-G-C		Inborn genetic diseases	Uncertain significance (Nov 27, 2024)
12-49295390-C-T		Amyotrophic lateral sclerosis	Uncertain significance (Mar 31, 2020)
12-49295390-C-CGAGCGG			Uncertain significance (Jul 28, 2022)
12-49295399-G-C		Inborn genetic diseases	Uncertain significance (Oct 17, 2024)
12-49295428-GC-G		Amyotrophic lateral sclerosis, susceptibility to	risk factor (Oct 29, 2004)
12-49295438-T-G		Inborn genetic diseases	Uncertain significance (Aug 14, 2024)
12-49295441-T-C		Inborn genetic diseases	Uncertain significance (Sep 09, 2024)
12-49295448-C-T			Uncertain significance (Apr 16, 2021)
12-49295456-C-T			Uncertain significance (Mar 22, 2023)
12-49295512-CA-C			Uncertain significance (Oct 31, 2022)
12-49295526-C-T		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
12-49295552-C-A			Benign (Aug 02, 2018)
12-49295564-A-G		Amyotrophic lateral sclerosis type 1	Uncertain significance (-)
12-49295583-A-T		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
12-49295594-G-A		Inborn genetic diseases	Uncertain significance (Apr 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRPH	protein_coding	protein_coding	ENST00000257860	9	5431

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.79e-14	0.0264	124482	6	1260	125748	0.00505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.556	245	271	0.905	0.0000141	2987
Missense in Polyphen		98	102.02	0.96057		1111
Synonymous	0.163	121	123	0.981	0.00000620	965
Loss of Function	0.171	21	21.9	0.961	0.00000100	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.000999
Ashkenazi Jewish	0.00	0.00
East Asian	0.000986	0.000979
Finnish	0.0223	0.0221
European (Non-Finnish)	0.00631	0.00630
Middle Eastern	0.000986	0.000979
South Asian	0.000766	0.000752
Other	0.00261	0.00261

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Class-III neuronal intermediate filament protein.
• Pathway: Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) (Consensus)

Recessive Scores

• pRec: 0.412

Intolerance Scores

• loftool: 0.394
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.45

Haploinsufficiency Scores

• pHI: 0.188
• hipred: Y
• hipred_score: 0.591
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.769

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prph
• 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)

Gene ontology

• Cellular component: intermediate filament;membrane;type III intermediate filament;extracellular exosome
• Molecular function: structural molecule activity;protein binding