RBP4

retinol binding protein 4, the group of Lipocalins

Basic information

Region (hg38): 10:93591687-93601744

Links

ENSG00000138207 ∙ NCBI:5950 ∙ OMIM:180250 ∙ HGNC:9922 ∙ Uniprot:P02753 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microphthalmia, isolated, with coloboma 10 (Strong), mode of inheritance: AD
• microphthalmia, isolated, with coloboma (Supportive), mode of inheritance: AD
• progressive retinal dystrophy due to retinol transport defect (Supportive), mode of inheritance: AR
• microphthalmia, isolated, with coloboma 10 (Moderate), mode of inheritance: AR
• progressive retinal dystrophy due to retinol transport defect (Definitive), mode of inheritance: AR
• microphthalmia, isolated, with coloboma 10 (Strong), mode of inheritance: AD
• progressive retinal dystrophy due to retinol transport defect (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia/coloboma 10; Retinol dystrophy, iris coloboma, and comedogenic acne syndrome	AD/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	Dermatologic; Ophthalmologic	9888420; 2886863; 1293390; 23189188; 25910211
It has been suggested that high-dose vitamin A supplementation may be beneficial in Retinol dystrophy, iris coloboma, and comedogenic acne syndrome

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RBP4 gene.

• not provided (4 variants)
• Bilateral microphthalmos (1 variants)
• Progressive retinal dystrophy due to retinol transport defect (1 variants)
• Microphthalmia, isolated, with coloboma 10 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RBP4 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				40	1	41
missense	1	9	66			76
nonsense	3					3
start loss			1			1
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3				4
splice region			6	2		8
non coding				14	16	30
Total	6	12	67	54	17

Highest pathogenic variant AF is 0.00000657

Variants in RBP4

This is a list of pathogenic ClinVar variants found in the RBP4 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-93592093-T-C			Likely benign (May 21, 2023)
10-93592104-C-T			Uncertain significance (Aug 31, 2020)
10-93592105-G-A			Likely benign (Aug 14, 2023)
10-93592113-C-T		Microphthalmia, isolated, with coloboma 10	Likely pathogenic (May 15, 2020)
10-93592121-T-TA			Likely benign (Oct 05, 2022)
10-93592193-A-G			Benign (May 25, 2021)
10-93593731-C-T			Benign (May 15, 2021)
10-93593756-G-A			Benign (May 15, 2021)
10-93593813-C-T			Likely benign (Mar 09, 2021)
10-93593816-G-T			Likely benign (Nov 15, 2022)
10-93593818-C-A			Uncertain significance (Aug 10, 2020)
10-93593818-C-G			Uncertain significance (Mar 18, 2023)
10-93593823-C-T			Uncertain significance (Oct 09, 2023)
10-93593824-G-A			Uncertain significance (Jan 15, 2024)
10-93593825-T-C		Inborn genetic diseases	Uncertain significance (Oct 24, 2023)
10-93593828-T-C			Uncertain significance (Apr 09, 2023)
10-93593832-C-T			Conflicting classifications of pathogenicity (Jan 12, 2024)
10-93593833-G-A			Likely benign (Nov 23, 2022)
10-93593847-G-T		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
10-93593848-C-T			Likely benign (Sep 15, 2022)
10-93593862-G-A			Likely benign (Dec 04, 2022)
10-93593863-C-A		Inborn genetic diseases	Uncertain significance (Jan 15, 2024)
10-93593865-C-A		Progressive retinal dystrophy due to retinol transport defect	Pathogenic (Mar 17, 2020)
10-93593868-C-T			Uncertain significance (Jul 05, 2022)
10-93593873-C-T			Uncertain significance (Dec 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RBP4	protein_coding	protein_coding	ENST00000371467	5	10058

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.520	0.477	125739	0	3	125742	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.775	98	122	0.803	0.00000758	1316
Missense in Polyphen		35	51.766	0.67611		561
Synonymous	0.000807	55	55.0	1.00	0.00000390	377
Loss of Function	2.45	2	10.6	0.189	5.07e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000180	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Retinol-binding protein that mediates retinol transport in blood plasma (PubMed:5541771). Delivers retinol from the liver stores to the peripheral tissues (Probable). Transfers the bound all-trans retinol to STRA6, that then facilitates retinol transport across the cell membrane (PubMed:22665496). {ECO:0000269|PubMed:22665496, ECO:0000305, ECO:0000305|PubMed:5541771}.
• Disease: DISEASE: Retinal dystrophy, iris coloboma, and comedogenic acne syndrome (RDCCAS) [MIM:615147]: A disease characterized by retinal degeneration, ocular colobomas involving both the anterior and posterior segment, impaired night vision and loss of visual acuity. Additional characteristic features include developmental abnormalities and severe acne. {ECO:0000269|PubMed:10232633, ECO:0000269|PubMed:23189188, ECO:0000269|PubMed:9888420}. Note=The disease is caused by mutations affecting the gene represented in this entry. Loss of functional RBP4 protein results in serum retinol deficiency. Lack of normal levels of retinol impairs the visual cycle leading to night blindness at early stages; prolonged deficiency may lead to retinal degeneration. Additionally, retinol deficiency may result in dry skin, increased susceptibility to infection and acne (PubMed:23189188). {ECO:0000269|PubMed:23189188}.; DISEASE: Microphthalmia, isolated, with coloboma, 10 (MCOPCB10) [MIM:616428]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). {ECO:0000269|PubMed:25910211}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Vitamin A and Carotenoid Metabolism;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism;The canonical retinoid cycle in rods (twilight vision);Metabolism of vitamins and cofactors;retinoate biosynthesis II;retinoate biosynthesis I;retinol biosynthesis;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;the visual cycle I (vertebrates);GPCR downstream signalling (Consensus)

Intolerance Scores

• loftool: 0.159
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.04

Haploinsufficiency Scores

• pHI: 0.514
• hipred: Y
• hipred_score: 0.830
• ghis: 0.962

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rbp4
• Phenotype: renal/urinary system phenotype; skeleton phenotype; vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; 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); reproductive system phenotype; normal phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: rbp4
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: retinoid metabolic process;eye development;gluconeogenesis;heart development;visual perception;maintenance of gastrointestinal epithelium;lung development;positive regulation of insulin secretion;response to retinoic acid;retinol transport;retinol metabolic process;glucose homeostasis;response to ethanol;embryonic organ morphogenesis;embryonic skeletal system development;cardiac muscle tissue development;female genitalia morphogenesis;positive regulation of immunoglobulin secretion;negative regulation of cardiac muscle cell proliferation;embryonic retina morphogenesis in camera-type eye;uterus development;vagina development;urinary bladder development;heart trabecula formation
• Cellular component: extracellular region;extracellular space;cytosol;protein-containing complex;extracellular exosome
• Molecular function: protein binding;retinal binding;retinol binding;retinol transmembrane transporter activity;protein heterodimerization activity