PAM16

presequence translocase associated motor 16, the group of TIM23 complex

Basic information

Region (hg38): 16:4331549-4355607

Links

ENSG00000217930 ∙ NCBI:51025 ∙ OMIM:614336 ∙ HGNC:29679 ∙ Uniprot:Q9Y3D7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spondylometaphyseal dysplasia, Megarbane type (Limited), mode of inheritance: AR
• autosomal recessive spondylometaphyseal dysplasia, Megarbane type (Strong), mode of inheritance: AR
• autosomal recessive spondylometaphyseal dysplasia, Megarbane type (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondylometaphyseal dysplasia, Megarbane-Dagher-Melki type	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	Musculoskeletal; Neurologic	18925669; 24458487; 24786642

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAM16 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAM16 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	10		11
missense			23		2	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	3	2	6
non coding			1	15	14	30
Total	0	0	25	25	16

Variants in PAM16

This is a list of pathogenic ClinVar variants found in the PAM16 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-4332064-T-C			Benign (Jul 14, 2018)
16-4332270-G-A		not specified • Nephronophthisis 7	Benign (Jul 05, 2018)
16-4332272-C-G			Uncertain significance (Jul 18, 2014)
16-4332295-C-T		GLIS2-related disorder	Uncertain significance (May 07, 2014)
16-4332298-G-A		Nephronophthisis	Likely benign (Mar 15, 2017)
16-4332331-C-G		Nephronophthisis	Likely benign (Oct 17, 2022)
16-4332336-C-T		Nephronophthisis 7 • Nephronophthisis	Uncertain significance (Nov 13, 2022)
16-4332337-G-A		Nephronophthisis	Likely benign (Oct 27, 2022)
16-4332337-G-T			Likely benign (Feb 09, 2018)
16-4332350-C-A		Nephronophthisis • not specified • Nephronophthisis 7	Benign/Likely benign (Mar 01, 2024)
16-4332351-G-A		not specified	Uncertain significance (Jun 29, 2022)
16-4332360-C-T		not specified	Uncertain significance (Mar 21, 2023)
16-4332380-C-T		Nephronophthisis	Uncertain significance (Sep 01, 2021)
16-4332381-G-A		Nephronophthisis • Nephronophthisis 7	Uncertain significance (Jul 06, 2022)
16-4332406-G-A		Nephronophthisis	Likely benign (Feb 06, 2023)
16-4332407-G-A		Nephronophthisis 7	Uncertain significance (Jan 13, 2018)
16-4332409-G-A		Nephronophthisis	Likely benign (Oct 22, 2023)
16-4332444-C-T		Nephronophthisis	Uncertain significance (Mar 09, 2021)
16-4332445-G-A		Nephronophthisis	Likely benign (Aug 02, 2023)
16-4332466-G-A		Nephronophthisis	Likely benign (Feb 23, 2023)
16-4332606-T-G			Benign (Jul 09, 2018)
16-4332652-G-T			Benign (Jul 10, 2018)
16-4333330-C-G		Nephronophthisis	Likely benign (May 09, 2022)
16-4333331-T-C		Nephronophthisis	Benign (Jan 08, 2024)
16-4333369-C-T		Nephronophthisis	Likely benign (May 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAM16	protein_coding	protein_coding	ENST00000318059	5	24059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.235	0.735	125499	0	7	125506	0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.511	94	81.1	1.16	0.00000540	793
Missense in Polyphen		25	25.548	0.97856		284
Synonymous	0.0118	33	33.1	0.997	0.00000214	244
Loss of Function	1.82	2	7.32	0.273	3.96e-7	81

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000499	0.0000462
European (Non-Finnish)	0.0000382	0.0000353
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates ATP-dependent protein translocation into the mitochondrial matrix. Inhibits DNAJC19 stimulation of HSPA9/Mortalin ATPase activity. {ECO:0000269|PubMed:20053669}.
• Disease: DISEASE: Spondylometaphyseal dysplasia, Megarbane-Dagher-Melike type (SMDMDM) [MIM:613320]: An autosomal recessive disease characterized by pre- and postnatal short stature, developmental delay, dysmorphic facial appearance, narrow chest, prominent abdomen, platyspondyly, and short limbs. {ECO:0000269|PubMed:24786642}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of proteins;Mitochondrial protein import (Consensus)

Intolerance Scores

• rvis_EVS: 0.39
• rvis_percentile_EVS: 75.87

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.491
• ghis: 0.459

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pam16
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: ossification;protein import into mitochondrial matrix;negative regulation of ATPase activity;negative regulation of release of cytochrome c from mitochondria;negative regulation of apoptotic DNA fragmentation
• Cellular component: PAM complex, Tim23 associated import motor;TIM23 mitochondrial import inner membrane translocase complex;mitochondrial matrix;extrinsic component of mitochondrial inner membrane;protein-containing complex
• Molecular function: protein binding