SORD

sorbitol dehydrogenase

Basic information

Region (hg38): 15:45023147-45077185

Links

ENSG00000140263 ∙ NCBI:6652 ∙ OMIM:182500 ∙ HGNC:11184 ∙ Uniprot:Q00796 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronopathy, distal hereditary motor, autosomal recessive 8 (Moderate), mode of inheritance: AR
• neuronopathy, distal hereditary motor, autosomal recessive 8 (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, autosomal recessive 8	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	Audiologic/Otolaryngologic; Biochemical; Musculoskeletal; Neurologic	32367058

ClinVar

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

• not_provided (48 variants)
• Inborn_genetic_diseases (46 variants)
• Neuronopathy,_distal_hereditary_motor,_autosomal_recessive_8 (18 variants)
• not_specified (5 variants)
• Idiopathic_environmental_intolerance (1 variants)
• Neuromuscular_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SORD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003104.6. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	12	5	18
missense	2	4	55	4	2	67
nonsense	2	2				4
start loss						0
frameshift	1	2	2			5
splice donor/acceptor (+/-2bp)	1					1
Total	6	8	58	16	7

Highest pathogenic variant AF is 0.0031969629

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SORD	protein_coding	protein_coding	ENST00000267814	9	54082

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.49e-8	0.382	125678	0	70	125748	0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.351	185	172	1.08	0.00000953	2254
Missense in Polyphen		62	62.735	0.98829		746
Synonymous	-0.588	75	68.8	1.09	0.00000406	729
Loss of Function	0.739	13	16.2	0.802	0.00000104	204

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.00111
Ashkenazi Jewish	0.000237	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000234	0.000229
Middle Eastern	0.00	0.00
South Asian	0.000269	0.000261
Other	0.000340	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts sorbitol to fructose. Part of the polyol pathway that plays an important role in sperm physiology. May play a role in the sperm motility by providing an energetic source for sperm. {ECO:0000250|UniProtKB:Q64442, ECO:0000269|PubMed:16278369}.
• Pathway: Fructose and mannose metabolism - Homo sapiens (human);Pentose and glucuronate interconversions - Homo sapiens (human);Fructose intolerance, hereditary;Fructose and Mannose Degradation;Fructosuria;Polyol Pathway;Fructose biosynthesis;Fructose metabolism;Metabolism of carbohydrates;Fructose Mannose metabolism;Metabolism;sorbitol degradation I;Catabolism of glucuronate to xylulose-5-phosphate (Consensus)

Recessive Scores

• pRec: 0.603

Intolerance Scores

• loftool: 0.766
• rvis_EVS: 0.86
• rvis_percentile_EVS: 88.74

Haploinsufficiency Scores

• pHI: 0.490
• hipred: N
• hipred_score: 0.343
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.607

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sord
• Phenotype: normal phenotype; vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: glucose metabolic process;sorbitol catabolic process;response to osmotic stress;response to hormone;glucuronate catabolic process to xylulose 5-phosphate;flagellated sperm motility;response to nutrient levels;response to drug;fructose biosynthetic process;response to cadmium ion;response to copper ion;L-xylitol catabolic process;L-xylitol metabolic process;oxidation-reduction process
• Cellular component: extracellular space;cytosol;membrane;motile cilium;mitochondrial membrane;extracellular exosome
• Molecular function: L-iditol 2-dehydrogenase activity;zinc ion binding;carbohydrate binding;identical protein binding;D-xylulose reductase activity;NAD binding