MIP

major intrinsic protein of lens fiber, the group of Aquaporins

Basic information

Region (hg38): 12:56449502-56469166

Links

ENSG00000135517

∙ NCBI:4284 ∙ OMIM:154050 ∙ HGNC:7103 ∙ Uniprot:P30301 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cataract 15 multiple types (Strong), mode of inheritance: AD
early-onset sutural cataract (Supportive), mode of inheritance: AD
cerulean cataract (Supportive), mode of inheritance: AD
early-onset nuclear cataract (Supportive), mode of inheritance: AD
early-onset posterior polar cataract (Supportive), mode of inheritance: AD
total early-onset cataract (Supportive), mode of inheritance: AD
early-onset lamellar cataract (Supportive), mode of inheritance: AD
cataract 15 multiple types (Definitive), mode of inheritance: AD
cataract 15 multiple types (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 15, multiple types	AD	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	10802646

ClinVar

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

Cataract_15_multiple_types (33 variants)
Inborn_genetic_diseases (27 variants)
not_provided (16 variants)
Developmental_cataract (6 variants)
MIP-related_disorder (3 variants)
Cataract (1 variants)
Microcornea (1 variants)
Persistent_hyperplastic_primary_vitreous (1 variants)
not_specified (1 variants)
Nystagmus (1 variants)
Microphthalmia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MIP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012064.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar	1 clinvar	4
missense	4 clinvar	2 clinvar	38 clinvar	2 clinvar	1 clinvar	47
nonsense	3 clinvar					3
start loss						0
frameshift	4 clinvar	4 clinvar	1 clinvar			9
splice donor/acceptor (+/-2bp)	2 clinvar	3 clinvar				5
Total	13	9	40	4	2

Highest pathogenic variant AF is 0.0000102611675

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MIP	protein_coding	protein_coding	ENST00000257979	4	19665

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0310	0.930	125735	0	12	125747	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	114	156	0.730	0.00000894	1669
Missense in Polyphen		39	67.332	0.57922		732
Synonymous	0.627	62	68.6	0.904	0.00000422	609
Loss of Function	1.78	4	10.1	0.396	6.03e-7	93

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000909	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Water channel (PubMed:24120416). Channel activity is down-regulated by CALM when cytoplasmic Ca(2+) levels are increased. May be responsible for regulating the osmolarity of the lens. Interactions between homotetramers from adjoining membranes may stabilize cell junctions in the eye lens core (By similarity). Plays a role in cell-to-cell adhesion and facilitates gap junction coupling (PubMed:24120416). {ECO:0000250|UniProtKB:Q6J8I9, ECO:0000269|PubMed:24120416}.;
Disease: DISEASE: Cataract 15, multiple types (CTRCT15) [MIM:615274]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT15 includes polymorphic, progressive punctate lamellar, cortical, anterior and posterior polar, nonprogressive lamellar with sutural opacities, embryonic nuclear, and pulverulent cortical, among others. {ECO:0000269|PubMed:10802646, ECO:0000269|PubMed:11001937, ECO:0000269|PubMed:16564824, ECO:0000269|PubMed:17893667, ECO:0000269|PubMed:17960133, ECO:0000269|PubMed:20361015, ECO:0000269|PubMed:21245956, ECO:0000269|PubMed:23116563, ECO:0000269|PubMed:24120416, ECO:0000269|PubMed:25946197}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Transport of small molecules;Passive transport by Aquaporins;Aquaporin-mediated transport (Consensus)

Recessive Scores

pRec: 0.145

Intolerance Scores

loftool: 0.195
rvis_EVS: 0.15
rvis_percentile_EVS: 64.32

Haploinsufficiency Scores

pHI: 0.184
hipred: Y
hipred_score: 0.704
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mip
Phenotype: vision/eye phenotype;

Zebrafish Information Network

Gene name: mipb
Affected structure: lens
Phenotype tag: abnormal
Phenotype quality: opaque

Gene ontology

Biological process: lens development in camera-type eye;water transport;visual perception;positive regulation of cell adhesion;response to stimulus;protein homotetramerization;transmembrane transport;gap junction-mediated intercellular transport
Cellular component: endoplasmic reticulum;plasma membrane;integral component of plasma membrane;gap junction;integral component of membrane;apical plasma membrane
Molecular function: structural constituent of eye lens;calmodulin binding;water channel activity