LMBR1

limb development membrane protein 1

Basic information

Region (hg38): 7:156668945-156893216

Previous symbols: [ "C7orf2" ]

Links

ENSG00000105983 ∙ NCBI:64327 ∙ OMIM:605522 ∙ HGNC:13243 ∙ Uniprot:Q8WVP7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acheiropody (Supportive), mode of inheritance: AR
• laurin-Sandrow syndrome (Supportive), mode of inheritance: AD
• triphalangeal thumb-polysyndactyly syndrome (Supportive), mode of inheritance: AD
• hypoplastic tibiae-postaxial polydactyly syndrome (Supportive), mode of inheritance: AD
• polydactyly of a triphalangeal thumb (Supportive), mode of inheritance: AD
• syndactyly type 4 (Supportive), mode of inheritance: AD
• acheiropody (Strong), mode of inheritance: AR
• polydactyly of a triphalangeal thumb (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Acheiropody; Syndactyly, type IV; Laurin-Sandrow syndrome; Triphalangeal thumb, type I; Polydactyly, preaxial type II; Triphalangeal thumb with polysyndactyly; Tibia, hypoplasia or aplasia of, with polydactyly	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	Craniofacial; Musculoskeletal	5808544; 1132167; 1155460; 1163539; 6660253; 10937618; 10780921; 11090342; 12837695; 16059937; 17152067; 17476456; 17300748; 18463159; 18178630; 18417549; 19291772; 20068592; 20569257; 22495965; 24456159; 24965254
Some conditions may be due to variants in ZRS, a SHH-regulatory element within an LMBR1 intron

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMBR1 gene.

• not provided (5 variants)
• Triphalangeal thumb (3 variants)
• Polydactyly of a triphalangeal thumb (3 variants)
• Tibia, hypoplasia or aplasia of, with polydactyly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMBR1 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			1	11	6	18
missense			28	1	3	32
nonsense	1		3			4
start loss						0
frameshift	1					1
inframe indel			2			2
splice donor/acceptor (+/-2bp)		2				2
splice region				4	1	5
non coding	3	1	148	76	121	349
Total	5	3	182	88	130

Highest pathogenic variant AF is 0.00000657

Variants in LMBR1

This is a list of pathogenic ClinVar variants found in the LMBR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-156675698-C-G		not specified	Uncertain significance (Sep 28, 2022)
7-156675700-C-T		not specified	Uncertain significance (Mar 07, 2024)
7-156675706-T-C		not specified	Uncertain significance (Jun 16, 2024)
7-156675733-A-C		not specified	Uncertain significance (Jun 11, 2021)
7-156675765-G-A		not specified	Uncertain significance (Feb 27, 2023)
7-156675814-A-T		not specified	Uncertain significance (Sep 23, 2023)
7-156675816-T-C		not specified	Uncertain significance (Jun 09, 2022)
7-156676426-G-A		not specified	Likely benign (May 14, 2024)
7-156676488-G-A		not specified	Uncertain significance (Nov 07, 2022)
7-156676504-G-A		not specified	Uncertain significance (Jul 19, 2023)
7-156676519-C-T		not specified	Likely benign (Dec 16, 2023)
7-156676552-C-T		not specified	Uncertain significance (Jan 08, 2024)
7-156676581-G-A		not specified	Uncertain significance (Sep 01, 2021)
7-156676637-G-T		not specified	Uncertain significance (Apr 14, 2022)
7-156676644-C-T		not specified	Uncertain significance (Sep 01, 2021)
7-156680871-A-C		Polydactyly of a triphalangeal thumb	Benign (Jan 12, 2018)
7-156680891-T-C		Polydactyly of a triphalangeal thumb	Uncertain significance (Jan 12, 2018)
7-156680898-T-G		Polydactyly of a triphalangeal thumb	Uncertain significance (Jan 13, 2018)
7-156681085-T-TA		Triphalangeal thumb-polysyndactyly syndrome	Benign (Jun 14, 2016)
7-156681130-C-A		Polydactyly of a triphalangeal thumb	Uncertain significance (Jan 12, 2018)
7-156681152-C-G		Polydactyly of a triphalangeal thumb	Benign (Jan 13, 2018)
7-156681173-A-T		Polydactyly of a triphalangeal thumb	Benign (Jan 13, 2018)
7-156681179-T-A		Polydactyly of a triphalangeal thumb	Uncertain significance (Jan 12, 2018)
7-156681258-C-T		Polydactyly of a triphalangeal thumb	Benign (Jan 12, 2018)
7-156681280-G-A		Polydactyly of a triphalangeal thumb	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMBR1	protein_coding	protein_coding	ENST00000353442	17	224279

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.26e-8	0.987	125641	0	106	125747	0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.849	206	243	0.847	0.0000122	3128
Missense in Polyphen		85	108.02	0.7869		1425
Synonymous	0.197	89	91.4	0.974	0.00000505	942
Loss of Function	2.33	18	32.3	0.557	0.00000194	382

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000491	0.000489
Ashkenazi Jewish	0.000605	0.000595
East Asian	0.000232	0.000217
Finnish	0.0000934	0.0000924
European (Non-Finnish)	0.000651	0.000633
Middle Eastern	0.000232	0.000217
South Asian	0.000287	0.000261
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Putative membrane receptor.
• Disease: DISEASE: Acheiropody (ACHP) [MIM:200500]: Very rare condition characterized by bilateral congenital amputations of the hands and feet. The specific malformative phenotype consists of a complete amputation of the distal epiphysis of the humerus, amputation of the tibial diaphysis and aplasia of the radius, ulna, fibula and of all the bones of the hands and feet. {ECO:0000269|PubMed:11090342}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Syndactyly 4 (SDTY4) [MIM:186200]: A form of syndactyly, a congenital anomaly of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached. SDTY4 is characterized by complete bilateral syndactyly (involving all digits 1 to 5). A frequent association with polydactyly (with six metacarpals and six digits) has been reported. Feet are affected occasionally. {ECO:0000269|PubMed:18417549, ECO:0000269|PubMed:24456159}. Note=The disease is caused by mutations affecting the gene represented in this entry. Disease-causing mutations consists of duplications (89-589 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis-regulatory element, located in LMBR1 intron 5. The mutations do not alter normal LMBR1 expression and function, but affect SHH limb expression. {ECO:0000269|PubMed:24456159}.; DISEASE: Hypoplasia or aplasia of tibia with polydactyly (THYP) [MIM:188740]: An autosomal dominant disease characterized by hypoplastic or absent tibia, and polydactyly. {ECO:0000269|PubMed:19847792, ECO:0000269|PubMed:24777739, ECO:0000269|PubMed:24965254}. Note=The disease is caused by mutations affecting the gene represented in this entry. Disease- causing mutations are located in intron 5 of LMBR1. The mutations do not alter normal LMBR1 expression and function, but disrupt a long-range, cis-regulatory element of SHH expression contained in LMBR1 intron 5. {ECO:0000269|PubMed:19847792, ECO:0000269|PubMed:24777739, ECO:0000269|PubMed:24965254}.; DISEASE: Laurin-Sandrow syndrome (LSS) [MIM:135750]: A rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. Some patients do not have nasal abnormalities (segmental Laurin-Sandrow syndrome). {ECO:0000269|PubMed:24456159}. Note=The disease is caused by mutations affecting the gene represented in this entry. Disease-causing mutations consists of duplications (16-75 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis- regulatory element, located in LMBR1 intron 5. The mutations do not alter normal LMBR1 expression and function, but affect SHH limb expression. {ECO:0000269|PubMed:24456159}.

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.798
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.247
• hipred: N
• hipred_score: 0.492
• ghis: 0.662

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.471

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lmbr1
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; normal 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); growth/size/body region phenotype

Gene ontology

• Biological process: embryonic digit morphogenesis
• Cellular component: integral component of membrane