SUN5

Sad1 and UNC84 domain containing 5, the group of SUN family

Basic information

Region (hg38): 20:32983772-33004433

Previous symbols: [ "SPAG4L" ]

Links

ENSG00000167098 ∙ NCBI:140732 ∙ OMIM:613942 ∙ HGNC:16252 ∙ Uniprot:Q8TC36 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 16 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 16	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	Genitourinary	27640305

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUN5 gene.

• Inborn genetic diseases (14 variants)
• not provided (4 variants)
• Spermatogenic failure 16 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUN5 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			1
missense		1	14			15
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	0	2	15	0	0

Highest pathogenic variant AF is 0.0000131

Variants in SUN5

This is a list of pathogenic ClinVar variants found in the SUN5 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-32983828-T-G		not specified	Uncertain significance (Nov 18, 2022)
20-32983859-C-G		not specified	Uncertain significance (Jun 29, 2023)
20-32983866-G-A		SUN5-related disorder	Likely benign (Aug 01, 2019)
20-32983868-G-A		Spermatogenic failure 16	Likely pathogenic (Mar 01, 2020)
20-32985091-G-A			Uncertain significance (Sep 01, 2021)
20-32985782-G-C		Spermatogenic failure 16	Pathogenic (Nov 07, 2016)
20-32985789-T-A		not specified	Uncertain significance (Apr 07, 2022)
20-32985809-G-A		Spermatogenic failure 16	Pathogenic (Nov 07, 2016)
20-32985852-C-T		Spermatogenic failure 16	Pathogenic (Nov 07, 2016)
20-32987715-T-C		not specified	Uncertain significance (Sep 16, 2021)
20-32987771-G-A			Uncertain significance (Mar 01, 2023)
20-32989681-T-G		not specified	Uncertain significance (Apr 12, 2022)
20-32989690-C-A		not specified	Uncertain significance (Apr 07, 2022)
20-32995668-A-T		Spermatogenic failure 16	Pathogenic (Nov 07, 2016)
20-32996330-C-T		not specified	Uncertain significance (Apr 26, 2023)
20-32997646-CT-C		Spermatogenic failure 16	Pathogenic/Likely pathogenic (Sep 01, 2021)
20-32997650-C-G		not specified	Uncertain significance (Mar 01, 2024)
20-32997651-A-G		not specified	Uncertain significance (Oct 14, 2021)
20-32997672-G-C		not specified	Uncertain significance (Apr 22, 2022)
20-33000076-A-G		not specified	Uncertain significance (Aug 16, 2022)
20-33001218-G-A		not specified	Uncertain significance (Aug 08, 2023)
20-33001239-G-A		not specified	Uncertain significance (Dec 15, 2022)
20-33001288-A-G		SUN5-related disorder	Likely benign (Apr 26, 2019)
20-33002596-C-T		not specified	Uncertain significance (Oct 20, 2023)
20-33002902-C-T		not specified	Uncertain significance (May 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUN5	protein_coding	protein_coding	ENST00000356173	13	20661

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.75e-14	0.0664	125621	1	126	125748	0.000505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.688	186	214	0.868	0.0000119	2488
Missense in Polyphen		63	76.742	0.82093		898
Synonymous	0.719	76	84.4	0.900	0.00000512	682
Loss of Function	0.572	22	25.1	0.877	0.00000132	261

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000344	0.000333
Ashkenazi Jewish	0.00139	0.00139
East Asian	0.00386	0.00381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.00386	0.00381
South Asian	0.000131	0.000131
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an essential role in anchoring sperm head to the tail. Is responsible for the attachment of the coupling apparatus to the sperm nuclear envelope. {ECO:0000305|PubMed:28541472, ECO:0000305|PubMed:28945193}.
• Disease: DISEASE: Spermatogenic failure 16 (SPGF16) [MIM:617187]: An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. Most spermatozoa are made up of headless tails, while a small proportion has an abnormal head-tail junction. A few spermatozoa are made up of tailless heads. {ECO:0000269|PubMed:27640305, ECO:0000269|PubMed:28541472, ECO:0000269|PubMed:28945193, ECO:0000269|PubMed:29298896}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0906

Intolerance Scores

• loftool: 0.833
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.71

Haploinsufficiency Scores

• pHI: 0.0922
• hipred: N
• hipred_score: 0.146
• ghis: 0.460

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.404

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sun5

Gene ontology

• Biological process: nuclear envelope organization;spermatogenesis;spermatid development;cytoskeletal anchoring at nuclear membrane
• Cellular component: nuclear envelope;nuclear inner membrane;Golgi apparatus;integral component of membrane;meiotic nuclear membrane microtubule tethering complex;sperm connecting piece
• Molecular function: molecular_function;protein membrane anchor