GeneBe

MIP

protein-coding

major intrinsic protein of lens fiber, the group of Aquaporins

Gene summary

Major intrinsic protein is a member of the water-transporting aquaporins as well as the original member of the MIP family of channel proteins. The function of the fiber cell membrane protein encoded by this gene is undetermined, yet this protein is speculated to play a role in intracellular communication. The MIP protein is expressed in the ocular lens and is required for correct lens function. This gene has been mapped among aquaporins AQP2, AQP5, and AQP6, in a potential gene cluster at 12q13. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012064.4

Inheritance

AD

ClinVar variants

P:33U:49B:6

Top phenotype

Cataract 15, multiple types

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr12:56,449,502-56,469,166

External References & Databases

Ensembl (ENSG00000135517)NCBI Gene (4284)OMIM (154050)HGNC:7103GenCCUniProt (P30301)AlphaFoldClinVar (MIP)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~19.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 15 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014110

Submitter: PanelApp Australia

cataract 15 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014110

Submitter: Labcorp Genetics (formerly Invitae)

early-onset posterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020378

Submitter: Orphanet

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

early-onset sutural cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020372

Submitter: Orphanet

cataract 15 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014110

Submitter: Ambry Genetics

cerulean cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020374

Submitter: Orphanet

early-onset lamellar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018611

Submitter: Orphanet

total early-onset cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021548

Submitter: Orphanet

cataract 15 multiple typesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0014110

Submitter: G2P

Clinical Genomic Database (CGD)

Cataract 15, multiple typesAD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 10802646Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MIP variants in ClinVar

10 Conditions Cataloged
Cataract 15 multiple typesTotal: 37
Inborn genetic diseasesTotal: 29
not providedTotal: 21
MIP-related disorderTotal: 15
Developmental cataractTotal: 6
not specifiedTotal: 2
MicrocorneaTotal: 1
Persistent hyperplastic primary vitreousTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012064.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
3
clinvar
 4
missense
3
clinvar
4
clinvar
46
clinvar
2
clinvar
1
clinvar
 56
nonsense
5
clinvar
2
clinvar
 7
start loss
0
frameshift
6
clinvar
7
clinvar
1
clinvar
 14
splice donor/acceptor (+/-2bp)
1
clinvar
5
clinvar
1
clinvar
 7
Total1518495188

Highest pathogenic variant AF is 0.0000102611675

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_012064.4RefSeqNP_036196.14MANE Select
ENST00000652304.1EnsemblENSP00000498622.14MANE Select
XM_011538354.2RefSeqXP_011536656.14Standard
XM_017019306.2RefSeqXP_016874795.14Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
mipbDanio rerio

Structure: lens

Quality: opaque

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Transport of small molecules
  • Passive transport by Aquaporins
  • Aquaporin-mediated transport

Biological Process

  • lens development in camera-type eye
  • water transport
  • visual perception
  • positive regulation of cell adhesion
  • response to stimulus

Molecular Function

  • structural constituent of eye lens
  • calmodulin binding
  • water channel activity

Cellular Component

  • endoplasmic reticulum
  • plasma membrane
  • integral component of plasma membrane
  • gap junction
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000257979
Coding exons
4
Length
19665
Individuals with no LoFs
125735
Homozygous LoFs
0
Heterozygous LoFs
12
Defined
125747
p
0.0000477
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.201141560.7300.000008941669
Missense (PolyPhen)3967.3320.57922732
Synonymous0.6276268.60.9040.00000422609
Loss of Function1.78410.10.3966.03e-793

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish0.0000920.000092rare
European (Non-Finnish)0.0000440.000044rare
South Asian00.0absent
Other0.000330.00033rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.145

Intolerance Scores

LoFtool
0.195
RVIS EVS
0.15
RVIS percentile EVS
64.32

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.801

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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