MBTPS1

membrane bound transcription factor peptidase, site 1, the group of Proprotein convertase subtilisin/kexin family

Basic information

Region (hg38): 16:84053761-84116942

Links

ENSG00000140943 ∙ NCBI:8720 ∙ OMIM:603355 ∙ HGNC:15456 ∙ Uniprot:Q14703 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepiphyseal dysplasia, kondo-fu type (Moderate), mode of inheritance: AR
• spondyloepiphyseal dysplasia, kondo-fu type (Moderate), mode of inheritance: AR
• spondyloepiphyseal dysplasia, kondo-fu type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepiphyseal dysplasia, Kondo-Fu 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	Craniofacial; Musculoskeletal; Ophthalmologic	30046013

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MBTPS1 gene.

• Spondyloepiphyseal dysplasia, kondo-fu type (2 variants)
• not provided (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MBTPS1 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			2	88	11	101
missense		2	163	12	2	179
nonsense	3	1				4
start loss						0
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			7	18	2	27
non coding			1	62	13	76
Total	3	4	167	162	26

Highest pathogenic variant AF is 0.00000657

Variants in MBTPS1

This is a list of pathogenic ClinVar variants found in the MBTPS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-84054442-C-T		MBTPS1-related disorder	Benign (Oct 17, 2019)
16-84054451-A-G		Spondyloepiphyseal dysplasia, kondo-fu type	Pathogenic (-)
16-84054456-G-A		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
16-84054459-G-T		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
16-84054471-G-A		Inborn genetic diseases	Uncertain significance (Jan 08, 2025)
16-84054481-G-C			Uncertain significance (Feb 19, 2024)
16-84054494-C-T			Likely benign (Jul 23, 2024)
16-84054497-G-A			Likely benign (Dec 15, 2024)
16-84054506-C-G			Uncertain significance (Aug 20, 2022)
16-84054519-C-T		Inborn genetic diseases	Uncertain significance (Dec 23, 2024)
16-84054524-C-T			Likely benign (Nov 13, 2023)
16-84054525-G-A			Uncertain significance (Dec 13, 2021)
16-84054559-A-G			Uncertain significance (Mar 11, 2022)
16-84054590-G-A			Likely benign (Nov 20, 2024)
16-84054630-C-T		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
16-84054631-G-A			Uncertain significance (May 07, 2022)
16-84054639-A-G		Inborn genetic diseases	Uncertain significance (Jan 21, 2025)
16-84054654-G-A			Likely benign (Sep 23, 2024)
16-84054657-C-T			Benign (Jan 27, 2025)
16-84054659-G-A			Likely benign (Jul 24, 2024)
16-84054662-G-A			Benign (Feb 03, 2025)
16-84054663-G-C			Benign (Feb 03, 2025)
16-84054664-T-C			Likely benign (Sep 10, 2023)
16-84055985-CA-C			Likely benign (Oct 09, 2024)
16-84055994-C-T			Likely benign (Jul 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MBTPS1	protein_coding	protein_coding	ENST00000343411	22	63144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.59e-9	1.00	125694	0	54	125748	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.45	715	614	1.16	0.0000353	6860
Missense in Polyphen		196	220.98	0.88697		2392
Synonymous	-2.42	291	243	1.20	0.0000154	2059
Loss of Function	4.08	24	57.4	0.418	0.00000302	642

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000690	0.000690
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000381	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000217	0.000211
Middle Eastern	0.000381	0.000381
South Asian	0.000175	0.000163
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease that catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs). Other known substrates are BDNF, GNPTAB and ATF6. Cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4. Cleaves known substrates after Arg- Ser-Val-Leu (SERBP-2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. {ECO:0000269|PubMed:21719679}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling;ATF6 (ATF6-alpha) activates chaperones;Post-translational protein phosphorylation;Metabolism of lipids;Unfolded Protein Response (UPR);Post-translational protein modification;Metabolism of proteins;Regulation of cholesterol biosynthesis by SREBP (SREBF);Metabolism;CREB3 factors activate genes;Transport of small molecules;Metabolism of steroids;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);srebp control of lipid synthesis;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling (Consensus)

Recessive Scores

• pRec: 0.502

Intolerance Scores

• loftool: 0.619
• rvis_EVS: -1.3
• rvis_percentile_EVS: 4.97

Haploinsufficiency Scores

• pHI: 0.262
• hipred: N
• hipred_score: 0.492
• ghis: 0.608

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.914

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mbtps1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; embryo phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; digestive/alimentary 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); reproductive system phenotype; hematopoietic system phenotype; pigmentation phenotype

Zebrafish Information Network

• Gene name: mbtps1
• Affected structure: pharyngeal arch 3-7
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: proteolysis;protein import into nucleus;lysosome organization;cholesterol metabolic process;endoplasmic reticulum unfolded protein response;membrane protein intracellular domain proteolysis;response to endoplasmic reticulum stress;ATF6-mediated unfolded protein response;post-translational protein modification;cellular protein metabolic process;regulation of cholesterol biosynthetic process
• Cellular component: Golgi membrane;endoplasmic reticulum lumen;endoplasmic reticulum membrane;Golgi apparatus;Golgi stack;integral component of membrane
• Molecular function: metalloendopeptidase activity;serine-type endopeptidase activity