LNPK

lunapark, ER junction formation factor

Basic information

Region (hg38): 2:175923882-176002839

Previous symbols: [ "KIAA1715" ]

Links

ENSG00000144320 ∙ NCBI:80856 ∙ OMIM:610236 ∙ HGNC:21610 ∙ Uniprot:Q9C0E8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum (Strong), mode of inheritance: AR
• neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	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	30032983

ClinVar

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

• Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LNPK 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	6	1	8
missense			9	4	1	14
nonsense		1	1			2
start loss						0
frameshift	1	2				3
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region			1	2		3
non coding			2	3	2	7
Total	2	3	13	13	4

Variants in LNPK

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

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

Position	Type	Phenotype	Significance	ClinVar
2-175930075-T-C		LNPK-related disorder	Likely benign (Apr 26, 2019)
2-175930096-T-C			Uncertain significance (Dec 01, 2023)
2-175930118-A-C			Likely benign (May 01, 2024)
2-175930144-T-C		Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	Uncertain significance (Dec 06, 2021)
2-175937343-C-G		Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	Pathogenic (Jun 03, 2020)
2-175937392-G-A			Likely benign (Feb 01, 2024)
2-175937467-T-C			Uncertain significance (Nov 21, 2022)
2-175937496-C-CA		Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	Likely pathogenic (Oct 31, 2022)
2-175937502-G-A		Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	Uncertain significance (Apr 09, 2020)
2-175937510-A-G		LNPK-related disorder	Likely benign (Oct 01, 2020)
2-175938341-C-T			Uncertain significance (May 16, 2023)
2-175939558-T-C		LNPK-related disorder	Uncertain significance (Dec 19, 2022)
2-175939607-G-A		Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	Uncertain significance (Mar 26, 2024)
2-175939613-G-A		Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	Pathogenic (Aug 17, 2018)
2-175939622-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 01, 2024)
2-175939637-GT-G		Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum	Pathogenic (Aug 17, 2018)
2-175941004-T-C		LNPK-related disorder	Benign (Jul 16, 2019)
2-175941013-C-T			Likely benign (Aug 01, 2024)
2-175941084-C-CA		LNPK-related disorder	Likely benign (Mar 22, 2019)
2-175947504-G-A			Uncertain significance (Oct 09, 2023)
2-175947562-TG-T			Pathogenic (Dec 14, 2022)
2-175947682-C-T			Likely benign (Jul 01, 2021)
2-175964387-C-T		Inborn genetic diseases	Uncertain significance (Nov 05, 2021)
2-175964389-G-C		LNPK-related disorder	Benign (Apr 27, 2019)
2-175964398-G-T			Uncertain significance (Apr 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LNPK	protein_coding	protein_coding	ENST00000272748	12	78948

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000622	0.999	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.549	189	211	0.894	0.00000993	2740
Missense in Polyphen		43	50.854	0.84556		664
Synonymous	-0.515	79	73.4	1.08	0.00000359	840
Loss of Function	2.90	10	25.9	0.386	0.00000148	319

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000582	0.0000582
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.00	0.00
South Asian	0.000135	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endoplasmic reticulum (ER)-shaping membrane protein that plays a role in determining ER morphology. Involved in the stabilization of nascent three-way ER tubular junctions within the ER network (PubMed:24223779, PubMed:25404289, PubMed:25548161, PubMed:27619977). May also play a role as a curvature-stabilizing protein within the three-way ER tubular junction network (PubMed:25404289). May be involved in limb and central nervous system development (By similarity). {ECO:0000250|UniProtKB:Q7TQ95, ECO:0000269|PubMed:24223779, ECO:0000269|PubMed:25404289, ECO:0000269|PubMed:25548161, ECO:0000269|PubMed:27619977}.

Recessive Scores

• pRec: 0.280

Intolerance Scores

• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.13

Haploinsufficiency Scores

• pHI: 0.0905
• hipred: N
• hipred_score: 0.426
• ghis: 0.507

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Lnpk
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; reproductive system 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: blood coagulation;regulation of chondrocyte differentiation;embryonic forelimb morphogenesis;embryonic digit morphogenesis;limb development;endoplasmic reticulum tubular network organization;endoplasmic reticulum tubular network maintenance;positive regulation of endoplasmic reticulum tubular network organization
• Cellular component: nucleoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;integral component of endoplasmic reticulum membrane;endoplasmic reticulum tubular network;endoplasmic reticulum tubular network membrane
• Molecular function: identical protein binding;metal ion binding