POP1

POP1 homolog, ribonuclease P/MRP subunit

Basic information

Region (hg38): 8:98117292-98159835

Links

ENSG00000104356 ∙ NCBI:10940 ∙ OMIM:602486 ∙ HGNC:30129 ∙ Uniprot:Q99575 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• anauxetic dysplasia 2 (Strong), mode of inheritance: AR
• anauxetic dysplasia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anauxetic dysplasia 2	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	Craniofacial; Musculoskeletal; Neurologic	21455487; 27380734; 28067412

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POP1 gene.

• not provided (261 variants)
• Inborn genetic diseases (48 variants)
• Anauxetic dysplasia 2 (3 variants)
• POP1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POP1 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			1	53	13	67
missense		1	120	8	7	136
nonsense	1	1	7			9
start loss						0
frameshift	1		4			5
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			5	4		9
non coding			1	15	42	58
Total	2	3	133	76	62

Variants in POP1

This is a list of pathogenic ClinVar variants found in the POP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-98123209-A-G			Benign (Nov 12, 2018)
8-98123342-C-G			Pathogenic (Jan 24, 2024)
8-98123345-A-G			Uncertain significance (Sep 17, 2023)
8-98123347-G-A			Benign (Jan 25, 2024)
8-98123347-G-C			Uncertain significance (Apr 13, 2021)
8-98123351-A-G			Uncertain significance (Apr 28, 2022)
8-98123364-C-T			Likely benign (Nov 11, 2022)
8-98123391-C-T			Likely benign (Jan 03, 2024)
8-98123401-C-T			Likely benign (Dec 17, 2022)
8-98123411-G-A		Inborn genetic diseases • POP1-related disorder	Conflicting classifications of pathogenicity (Jan 08, 2024)
8-98123467-G-C		Inborn genetic diseases	Uncertain significance (Nov 03, 2022)
8-98123475-A-G			Likely benign (Dec 07, 2022)
8-98123484-A-G			Uncertain significance (Apr 16, 2022)
8-98123559-A-G			Benign (Jun 19, 2021)
8-98123775-C-CA			Benign (Jun 20, 2021)
8-98127382-C-T			Benign (Nov 12, 2018)
8-98127590-A-G			Likely benign (Jan 02, 2024)
8-98127615-C-T			Conflicting classifications of pathogenicity (Nov 13, 2023)
8-98127616-G-A			Uncertain significance (Feb 12, 2022)
8-98127622-G-A		Inborn genetic diseases	Uncertain significance (Jun 04, 2022)
8-98127623-G-A			Benign (Nov 13, 2023)
8-98127646-C-G			Uncertain significance (Aug 20, 2022)
8-98127649-T-C		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
8-98127673-A-G			Benign (Jan 29, 2024)
8-98127674-G-A			Likely benign (Sep 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POP1	protein_coding	protein_coding	ENST00000401707	15	42538

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.81e-13	0.999	125569	0	179	125748	0.000712

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	495	570	0.868	0.0000332	6670
Missense in Polyphen		144	201.29	0.71539		2350
Synonymous	1.28	193	217	0.889	0.0000132	2026
Loss of Function	2.97	29	52.2	0.556	0.00000300	587

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00155	0.00155
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000489
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000891	0.000888
Middle Eastern	0.000489	0.000489
South Asian	0.00118	0.00114
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of RNase MRP.
• Disease: DISEASE: Anauxetic dysplasia 2 (ANXD2) [MIM:617396]: An autosomal recessive spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability. {ECO:0000269|PubMed:21455487, ECO:0000269|PubMed:27380734, ECO:0000269|PubMed:28067412}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);RNA transport - Homo sapiens (human);tRNA processing;Metabolism of RNA;tRNA processing in the nucleus (Consensus)

Recessive Scores

• pRec: 0.0892

Intolerance Scores

• loftool: 0.969
• rvis_EVS: -1.23
• rvis_percentile_EVS: 5.54

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.467
• ghis: 0.595

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.850

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pop1

Gene ontology

• Biological process: tRNA 5'-leader removal;tRNA processing;tRNA catabolic process;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: ribonuclease MRP complex;extracellular space;nucleoplasm;nucleolar ribonuclease P complex;nucleolus;multimeric ribonuclease P complex
• Molecular function: ribonuclease MRP activity;RNA binding;ribonuclease P activity;protein binding