SUN5

protein-coding

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

Gene summary

The protein encoded by this gene appears to play a role in the meiotic stage of spermatogenesis. The encoded protein localizes to the junction between the sperm head and body and may be involved in nuclear envelope reconstitution and nuclear migration. Mutations in this gene have been implicated in acephalic spermatozoa syndrome. [provided by RefSeq, May 2017]

Previous symbols:

SPAG4L

MANE transcript

NM_080675.4

Inheritance

ClinVar variants

P:9U:54B:2

Top phenotype

Spermatogenic failure 16

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr20:32,983,773-33,004,433

External References & Databases

Ensembl (ENSG00000167098)

Transcript & Mutation Effects

hg38 • Region Span ~20.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 16STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014961

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure 16AR

Manifestation: Genitourinary

Intervention: General

Rationale: 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

Refs: 27640305

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUN5 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 54

Spermatogenic failure 16Total: 10

not providedTotal: 5

SUN5-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080675.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense	4 clinvar	1 clinvar	53 clinvar	1 clinvar		59
nonsense	1 clinvar	1 clinvar				2
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	6	3	54	2	0	65

Highest pathogenic variant AF is 0.00011709196

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080675.4	RefSeq	NP_542406.2	13	MANE Select
ENST00000356173.8	Ensembl	ENSP00000348496.3	13	MANE Select
ENST00000375519.2	Ensembl	ENSP00000364669.2	4	Standard
ENST00000375519.3	Ensembl	ENSP00000364669.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nuclear envelope organization
spermatogenesis
spermatid development
cytoskeletal anchoring at nuclear membrane

Molecular Function

molecular_function
protein membrane anchor

Cellular Component

nuclear envelope
nuclear inner membrane
Golgi apparatus
integral component of membrane
meiotic nuclear membrane microtubule tethering complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356173
Coding exons: 13
Length: 20661
Individuals with no LoFs: 125621
Homozygous LoFs: 1
Heterozygous LoFs: 126
Defined: 125748
p: 0.000505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.688	186	214	0.868	0.0000119	2488
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.0014	0.0014	notable
East Asian	0.0039	0.0038	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.00013	0.00013	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.404

Gene Damage Prediction

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