MAB21L2

mab-21 like 2, the group of MAB21 family

Basic information

Region (hg38): 4:150582151-150584693

Links

ENSG00000181541 ∙ NCBI:10586 ∙ OMIM:604357 ∙ HGNC:6758 ∙ Uniprot:Q9Y586 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• colobomatous microphthalmia-rhizomelic dysplasia syndrome (Definitive), mode of inheritance: AR
• colobomatous microphthalmia-rhizomelic dysplasia syndrome (Definitive), mode of inheritance: AD
• colobomatous microphthalmia-rhizomelic dysplasia syndrome (Strong), mode of inheritance: AD
• colobomatous microphthalmia-rhizomelic dysplasia syndrome (Moderate), mode of inheritance: Semidominant
• colobomatous microphthalmia-rhizomelic dysplasia syndrome (Strong), mode of inheritance: AD
• colobomatous microphthalmia-rhizomelic dysplasia syndrome (Supportive), mode of inheritance: AD
• colobomatous microphthalmia-rhizomelic dysplasia syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia/coloboma and skeletal dysplasia syndrome	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; Neurologic; Ophthalmologic	24906020

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAB21L2 gene.

• Colobomatous microphthalmia-rhizomelic dysplasia syndrome (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAB21L2 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				10	1	11
missense	1	4	8	1	1	15
nonsense	2	1	2			5
start loss		1				1
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	3	7	11	11	4

Variants in MAB21L2

This is a list of pathogenic ClinVar variants found in the MAB21L2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-150583030-A-C		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Likely pathogenic (May 15, 2020)
4-150583035-C-T			Likely benign (Dec 03, 2018)
4-150583036-G-A		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Uncertain significance (Aug 01, 2018)
4-150583077-C-T		MAB21L2-related disorder	Likely benign (Mar 24, 2023)
4-150583174-G-A		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Likely pathogenic (Jun 05, 2015)
4-150583180-C-G		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Pathogenic (Nov 10, 2023)
4-150583180-C-T		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Likely pathogenic (Jun 05, 2015)
4-150583181-G-A		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Likely pathogenic (Jun 05, 2015)
4-150583229-A-G		Inborn genetic diseases	Uncertain significance (Sep 24, 2021)
4-150583314-CGGCTGCGCA-C		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Uncertain significance (Feb 08, 2019)
4-150583344-G-C			Likely benign (Aug 14, 2023)
4-150583347-G-A			Likely benign (Nov 20, 2019)
4-150583349-A-G		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
4-150583351-C-G			Uncertain significance (Jan 21, 2024)
4-150583371-C-G			Likely benign (Sep 18, 2023)
4-150583372-G-T		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Uncertain significance (Jan 01, 2016)
4-150583389-G-C			Likely benign (Jul 11, 2018)
4-150583424-T-G			Likely benign (Feb 28, 2023)
4-150583434-G-T			Likely benign (May 20, 2023)
4-150583486-G-A		Colobomatous microphthalmia-rhizomelic dysplasia syndrome	Uncertain significance (Nov 26, 2020)
4-150583507-T-C			Benign (Jun 13, 2022)
4-150583511-G-GCATCAGGGCGCT			Uncertain significance (Aug 30, 2024)
4-150583527-T-G			Likely pathogenic (Feb 01, 2024)
4-150583675-T-A			Benign (Aug 24, 2023)
4-150583679-C-A			Uncertain significance (Jul 24, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAB21L2	protein_coding	protein_coding	ENST00000317605	1	2767

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.438	0.561	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.96	110	238	0.461	0.0000152	2315
Missense in Polyphen		33	91.381	0.36113		863
Synonymous	1.53	94	115	0.818	0.00000828	749
Loss of Function	2.74	3	14.1	0.213	7.98e-7	135

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for several aspects of embryonic development including normal development of the eye. {ECO:0000269|PubMed:24906020, ECO:0000269|PubMed:25719200}.
• Disease: DISEASE: Microphthalmia/coloboma and skeletal dysplasia syndrome (MCSKS) [MIM:615877]: A disease characterized by bilateral colobomatous microphthalmia or bilateral anophthalmia, associated with skeletal dysplasia in some cases. Additional ocular findings include microcornea, cataracts, corectopia and nystagmus. Intellectual disability is present in some patients. {ECO:0000269|PubMed:24906020, ECO:0000269|PubMed:25719200}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.221
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.680
• hipred: Y
• hipred_score: 0.818
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mab21l2
• Phenotype: vision/eye 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: mab21l2
• Affected structure: hyaloid vessel
• Phenotype tag: abnormal
• Phenotype quality: increased thickness

Gene ontology

• Biological process: eye development;nervous system development;positive regulation of cell population proliferation;embryonic body morphogenesis;camera-type eye development
• Cellular component: nucleus;cytoplasm
• Molecular function: protein binding