SDHD |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- SDHD (HGNC:10683) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- succinate dehydrogenase complex subunit D
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- PGL, PGL1
- Alias symbols
- cybS
- %HI
- 39.67(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.34(Read more about gnomAD pLI score)
- LOEUF
- 0.73(Read more about gnomAD LOEUF score)
- Cytoband
- 11q23.1
- Genomic Coordinates
-
GRCh37/hg19: chr11:111957597-111966518 NCBI Ensembl UCSC GRCh38/hg38: chr11:112086873-112095794 NCBI Ensembl UCSC - MANE Select Transcript
- NM_003002.4 ENST00000375549.8 (Read more about MANE Select)
- Function
- Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). {ECO:0000250}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-17890
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
08/11/2021
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- hereditary paragangliomas Monarch
HI Evidence:
-
PUBMED:
10657297
Baysal et al. 2000 describe SDHD variants in five families with hereditary paraganglioma, including two nonsense variants (p.E36X and p.R38X). The authors reported that none of the mutations had been observed in >200 normal control chromosomes and the mutations cosegregated with the disease phenotype in all affected individuals.
-
PUBMED:
12111639
Cascon et al. (2002) report variants in SDHD identified in individuals with paraganglioma and/or pheochromocytoma, including one nonsense variant (p.W43X) and one "4-bp frameshift deletion in codon 112 (13732delGACT)" resulting in a truncated protein of 132 amino acids.
-
PUBMED:
11343322
Milunsky et al. (2001) evaluated members of seven families with hereditary paragangliomas. Three loss of function variants were identified: 1) 1-bp insertion (13732insT) in exon 4 in affected members of an Italian family; 2) p.S32X in exon 2 in affected members of an English family; 3) 1-bp deletion (13838delG) in exon 4 in affected members of a German family.
-
PUBMED:
15531530
McWhinney et al. (2004) identified a ~96kb germline whole-gene deletion of SDHD in a 2-generation family with 6 affected individuals with pheochromocytoma and paraganglioma. The authors note that this region may also include part of the adjacent TIMM8B gene. They also identified a 1-kb deletion involving the 5' end of SDHD in another affected family.
-
PUBMED:
12000816
Neumann et al. (2002) identified two nonsense variants (p.C11Xand p.W5X) in the germline of a patient with sporadic pheochromocytoma. These two variants were not identified in 600 control chromosomes.
-
PUBMED:
18211978
Pigny et al. (2008) reported a family with maternal transmission of the p.W43X mutation in the third generation. A boy received the mutation from his mother and developed a glomus tympanicum paraganglioma at 11 years of age. He shared only the 11q23 haplotype with the other affected members of the family.
HI Evidence Comments:
Germline mutations of the SDHD gene show a ‘parent-of-origin’ expression phenotype, with tumor development occurring only when mutations are inherited via the paternal line. This phenotype was originally interpreted as evidence for ‘imprinted’ or allele-specific gene expression of SDHD. However, SDHD shows biallelic expression in brain, kidney and lymphoid tissues (Baysal et al., 2000). Moreover, consistent loss of the wild-type maternal allele in SDHD-linked tumors suggests expression of the maternal SDHD allele in normal paraganglia. Hensen et al. (2004) demonstrated exclusive loss of the entire maternal chromosome 11 in SDHD-linked paragangliomas and phaeochromocytomas, suggesting that combined loss of the wt SDHD allele and maternal 11p region is essential for tumorigenesis.
Bayley et al (2009) describe two patients with paraganglioma who are deleted for exons 1 and 2 of SDHD as well as the promoter. These deletions also included varying amounts of TIMM8B and other genes (PMID:19546167). Additionally, Caninanos et al (2011) describe one family with paraganglioma and a 25 kb deletion involving the promotor and exons 1 and 2 of SDHD, as well as 5 other genes (DLAT, PIH1D2, C11orf57, TIMM8B, SDHD) (PMID: 20310044).
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000011.9)
(NC_000011.10)