MAK

male germ cell associated kinase

Basic information

Region (hg38): 6:10762722-10838553

Links

ENSG00000111837 ∙ NCBI:4117 ∙ OMIM:154235 ∙ HGNC:6816 ∙ Uniprot:P20794 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 62 (Moderate), mode of inheritance: AR
• retinitis pigmentosa 62 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 62 (Definitive), mode of inheritance: AR
• inherited retinal dystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 62	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	Ophthalmologic	21835304

ClinVar

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

• not provided (390 variants)
• Retinitis Pigmentosa, Recessive (39 variants)
• Inborn genetic diseases (32 variants)
• Retinitis pigmentosa (18 variants)
• Retinitis pigmentosa 62 (15 variants)
• not specified (6 variants)
• Retinal dystrophy (6 variants)
• Isolated macular dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAK 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			5	70	3	78
missense	3	1	165	8	2	179
nonsense	10		2			12
start loss			1			1
frameshift	27	6	3			36
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)		9				9
splice region			10	11		21
non coding			23	46	9	78
Total	40	16	200	125	14

Highest pathogenic variant AF is 0.0000526

Variants in MAK

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

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

Position	Type	Phenotype	Significance	ClinVar
6-10762764-G-T		Retinitis Pigmentosa, Recessive	Benign (Jun 14, 2016)
6-10762889-C-T		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10763013-CAGT-C		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10763023-CATT-C		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10763079-G-A		Retinitis Pigmentosa, Recessive	Benign (Jun 14, 2016)
6-10763105-G-A		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10763486-G-A		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10763546-TA-T		Retinitis Pigmentosa, Recessive	Benign (Jun 14, 2016)
6-10763724-G-A		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10763850-C-CA		Retinitis Pigmentosa, Recessive	Likely benign (Jun 14, 2016)
6-10764119-C-CTA		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10764139-G-GTT		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10764173-T-G		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10764226-C-T		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10764418-G-A		Retinitis Pigmentosa, Recessive	Uncertain significance (Jun 14, 2016)
6-10764452-C-T			Likely benign (Oct 31, 2023)
6-10764455-C-T			Likely benign (Mar 09, 2023)
6-10764456-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2023)
6-10764457-G-A			Uncertain significance (Oct 19, 2021)
6-10764461-G-C			Likely benign (Jul 28, 2023)
6-10764469-A-G		Retinitis pigmentosa 62	Uncertain significance (Mar 30, 2023)
6-10764489-C-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2023)
6-10764491-C-T			Likely benign (Oct 26, 2023)
6-10764493-C-T		Inborn genetic diseases	Uncertain significance (Aug 01, 2022)
6-10764493-CA-TG			Uncertain significance (May 29, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAK	protein_coding	protein_coding	ENST00000313243	13	75809

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.63e-19	0.0155	125637	0	111	125748	0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.400	309	329	0.938	0.0000177	4078
Missense in Polyphen		102	114.21	0.89308		1461
Synonymous	1.04	104	118	0.879	0.00000679	1150
Loss of Function	0.599	30	33.8	0.889	0.00000163	429

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00109	0.00107
Ashkenazi Jewish	0.00	0.00
East Asian	0.000815	0.000816
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000451	0.000448
Middle Eastern	0.000815	0.000816
South Asian	0.000462	0.000457
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for the regulation of ciliary length and required for the long-term survival of photoreceptors (By similarity). Phosphorylates FZR1 in a cell cycle-dependent manner. Plays a role in the transcriptional coactivation of AR. Could play an important function in spermatogenesis. May play a role in chromosomal stability in prostate cancer cells. {ECO:0000250, ECO:0000269|PubMed:12084720, ECO:0000269|PubMed:16951154, ECO:0000269|PubMed:21986944}.
• Disease: DISEASE: Retinitis pigmentosa 62 (RP62) [MIM:614181]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:21825139, ECO:0000269|PubMed:21835304}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Coregulation of Androgen receptor activity (Consensus)

Recessive Scores

• pRec: 0.100

Intolerance Scores

• loftool: 0.962
• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.31

Haploinsufficiency Scores

• pHI: 0.213
• hipred: N
• hipred_score: 0.411
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.672

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mak
• Phenotype: reproductive system phenotype

Gene ontology

• Biological process: protein phosphorylation;multicellular organism development;spermatogenesis;regulation of gene expression;cell differentiation;intracellular signal transduction;intraciliary transport;photoreceptor cell maintenance;protein autophosphorylation;cilium assembly;negative regulation of non-motile cilium assembly;positive regulation of nucleic acid-templated transcription
• Cellular component: photoreceptor outer segment;photoreceptor inner segment;nucleus;cytoplasm;centrosome;cilium;axoneme;midbody;motile cilium;photoreceptor connecting cilium;mitotic spindle
• Molecular function: transcription coactivator activity;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;metal ion binding