KPTN

kaptin, actin binding protein, the group of KICSTOR complex

Basic information

Region (hg38): 19:47475150-47484265

Links

ENSG00000118162 ∙ NCBI:11133 ∙ OMIM:615620 ∙ HGNC:6404 ∙ Uniprot:Q9Y664 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• macrocephaly-developmental delay syndrome (Supportive), mode of inheritance: AR
• macrocephaly-developmental delay syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 41	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; Neurologic	24239382

ClinVar

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

• Macrocephaly-developmental delay syndrome (8 variants)
• not provided (2 variants)
• KPTN-related disorder (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KPTN 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				25	5	30
missense		1	74	3	1	79
nonsense	2	1				3
start loss						0
frameshift	5	3	2			10
inframe indel		1				1
splice donor/acceptor (+/-2bp)	2		1			3
splice region			6	8	1	15
non coding			2	12	8	22
Total	9	6	79	40	14

Highest pathogenic variant AF is 0.000105

Variants in KPTN

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

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

Position	Type	Phenotype	Significance	ClinVar
19-47475414-G-A			Benign (May 04, 2021)
19-47475420-G-A		Inborn genetic diseases	Uncertain significance (Jun 03, 2024)
19-47475422-G-A		Macrocephaly-developmental delay syndrome	Likely benign (Dec 09, 2024)
19-47475435-G-T		Macrocephaly-developmental delay syndrome	Uncertain significance (Mar 06, 2020)
19-47475446-A-G		Macrocephaly-developmental delay syndrome	Likely benign (Jul 17, 2024)
19-47475451-C-T		Inborn genetic diseases	Uncertain significance (May 31, 2023)
19-47475454-C-T		Inborn genetic diseases	Likely benign (Jun 03, 2022)
19-47475459-T-C		not specified • Macrocephaly-developmental delay syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 24, 2025)
19-47475464-C-T		Macrocephaly-developmental delay syndrome	Likely benign (Jul 12, 2022)
19-47475475-G-A		Inborn genetic diseases	Uncertain significance (Aug 19, 2024)
19-47475477-C-T		Macrocephaly-developmental delay syndrome • Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
19-47475479-T-C			Likely benign (Oct 01, 2024)
19-47475482-C-T		Macrocephaly-developmental delay syndrome	Benign (Jan 21, 2025)
19-47475484-T-C		Macrocephaly-developmental delay syndrome	Uncertain significance (Jun 13, 2022)
19-47475493-C-T		Macrocephaly-developmental delay syndrome	Uncertain significance (Feb 08, 2020)
19-47475502-G-A		Macrocephaly-developmental delay syndrome	Conflicting classifications of pathogenicity (Aug 11, 2019)
19-47475504-A-C		Inborn genetic diseases	Uncertain significance (Aug 19, 2024)
19-47475505-G-A		Macrocephaly-developmental delay syndrome	Uncertain significance (Jun 12, 2024)
19-47475529-C-A		Inborn genetic diseases	Uncertain significance (Dec 24, 2024)
19-47475538-GGCTGTGCTGTGGGGAACAAGAGAATGAGGGGGATGGAGCTGAGGAAGA-G		Inborn genetic diseases	Uncertain significance (Nov 03, 2021)
19-47475545-C-T		Macrocephaly-developmental delay syndrome	Pathogenic (May 04, 2022)
19-47475547-G-C		Macrocephaly-developmental delay syndrome	Uncertain significance (Mar 04, 2025)
19-47475552-GA-G		Macrocephaly-developmental delay syndrome	Likely benign (Jun 28, 2024)
19-47476524-G-A			Likely benign (Dec 15, 2017)
19-47476546-C-T		not specified • Inborn genetic diseases	Uncertain significance (Nov 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KPTN	protein_coding	protein_coding	ENST00000338134	12	9125

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000113	0.989	124726	0	84	124810	0.000337

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	200	266	0.751	0.0000154	2776
Missense in Polyphen		68	90.477	0.75157		1016
Synonymous	0.829	106	117	0.903	0.00000703	902
Loss of Function	2.28	12	24.0	0.499	0.00000122	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000571	0.000555
Ashkenazi Jewish	0.00	0.00
East Asian	0.000308	0.000278
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000522	0.000521
Middle Eastern	0.000308	0.000278
South Asian	0.0000981	0.0000980
Other	0.000330	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose. {ECO:0000269|PubMed:28199306}.
• Disease: DISEASE: Mental retardation, autosomal recessive 41 (MRT41) [MIM:615637]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT41 most consistent features are global developmental delay, macrocephaly with frontal bossing, high levels of anxiety, and some features suggestive of a pervasive developmental disorder. Less common features include fifth finger clinodactyly, recurrent pneumonia, and hepatosplenomegaly. {ECO:0000269|PubMed:24239382}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.441
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.43

Haploinsufficiency Scores

• pHI: 0.193
• hipred: N
• hipred_score: 0.378
• ghis: 0.555

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kptn
• Phenotype: immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: actin filament organization;cellular response to amino acid starvation;cellular response to glucose starvation;protein localization to lysosome;negative regulation of TORC1 signaling
• Cellular component: lysosomal membrane;lamellipodium;filamentous actin;stereocilium;postsynaptic actin cytoskeleton;KICSTOR complex
• Molecular function: actin filament binding