Mutagenetix > Incidental Mutation

Incidental Mutation 'R7089:Scnn1a'

550076

Institutional Source

Beutler Lab

Gene Symbol

Scnn1a

Ensembl Gene

ENSMUSG00000030340

Gene Name

sodium channel, nonvoltage-gated 1 alpha

Synonyms

Scnn1, mENaC, ENaC alpha

MMRRC Submission

045183-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7089 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

125297622-125321906 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 125314770 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Lysine at position 324 (Q324K)

Ref Sequence

ENSEMBL: ENSMUSP00000080164 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000081440] [ENSMUST00000175966] [ENSMUST00000176110] [ENSMUST00000176442] [ENSMUST00000176655] [ENSMUST00000177329]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000081440
AA Change: Q324K

PolyPhen 2 Score 0.048 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000080164
Gene: ENSMUSG00000030340
AA Change: Q324K

Domain	Start	End	E-Value	Type
low complexity region	13	18	N/A	INTRINSIC
Pfam:ASC	88	600	1.1e-93	PFAM
low complexity region	647	677	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000175966
AA Change: S234*

SMART Domains

Protein: ENSMUSP00000135551
Gene: ENSMUSG00000030340
AA Change: S234*

Domain	Start	End	E-Value	Type
Pfam:ASC	62	264	3.5e-28	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000176110
AA Change: Q298K

PolyPhen 2 Score 0.048 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000134940
Gene: ENSMUSG00000030340
AA Change: Q298K

Domain	Start	End	E-Value	Type
Pfam:ASC	62	575	1.9e-112	PFAM
low complexity region	621	651	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000176442
AA Change: Q217K

PolyPhen 2 Score 0.048 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000135336
Gene: ENSMUSG00000030340
AA Change: Q217K

Domain	Start	End	E-Value	Type
Pfam:ASC	1	494	6.3e-105	PFAM
low complexity region	540	570	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000176655
AA Change: Q217K

PolyPhen 2 Score 0.048 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000135798
Gene: ENSMUSG00000030340
AA Change: Q217K

Domain	Start	End	E-Value	Type
Pfam:ASC	1	494	6.4e-105	PFAM
low complexity region	540	570	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177329
AA Change: Q298K

PolyPhen 2 Score 0.048 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000134929
Gene: ENSMUSG00000030340
AA Change: Q298K

Domain	Start	End	E-Value	Type
Pfam:ASC	62	575	1.9e-112	PFAM
low complexity region	621	651	N/A	INTRINSIC

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.0%

Validation Efficiency

99% (68/69)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]
PHENOTYPE: Homozygotes for targeted null mutations exhibit skin with epithelial hyperplasia, abnormal nuclei, premature lipid secretion, and abnormal keratohyaline granules. Mutants die within 40 hours of birth due to inability to clear their lungs of liquid. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700010I14Rik	T	C	17: 9,226,927 (GRCm39)	V494A	probably benign	Het
1700017B05Rik	A	T	9: 57,166,041 (GRCm39)	L111Q	probably damaging	Het
Adgrf4	T	G	17: 42,977,424 (GRCm39)	I640L	possibly damaging	Het
Afdn	T	G	17: 14,111,074 (GRCm39)		probably null	Het
Ammecr1l	A	T	18: 31,894,877 (GRCm39)		probably benign	Het
Aox1	A	T	1: 58,375,808 (GRCm39)	Y879F	probably benign	Het
Arhgap45	G	A	10: 79,862,181 (GRCm39)		probably null	Het
Arpp21	G	T	9: 111,955,514 (GRCm39)	H542N	probably benign	Het
Ccdc192	C	T	18: 57,725,059 (GRCm39)	T96I	probably benign	Het
Cdt1	G	A	8: 123,298,719 (GRCm39)	R452Q	probably damaging	Het
Clcn7	C	T	17: 25,372,667 (GRCm39)	H149Y		Het
Clpp	T	G	17: 57,297,421 (GRCm39)	W32G	probably benign	Het
Dnmt1	G	T	9: 20,819,785 (GRCm39)	L1572M	probably damaging	Het
Drd3	G	T	16: 43,627,741 (GRCm39)	R128S	probably damaging	Het
Elmo2	A	T	2: 165,146,849 (GRCm39)	F243I	possibly damaging	Het
Endou	G	A	15: 97,618,126 (GRCm39)	P128L	probably benign	Het
Fat3	A	G	9: 15,908,214 (GRCm39)	M2596T	probably benign	Het
Fbxl16	A	G	17: 26,035,703 (GRCm39)	K100R	probably benign	Het
Fbxo10	A	G	4: 45,062,230 (GRCm39)	S99P	possibly damaging	Het
Fez1	A	T	9: 36,778,999 (GRCm39)	R225S	probably benign	Het
Gm14326	A	T	2: 177,588,464 (GRCm39)	H177Q	probably damaging	Het
Gm32742	T	A	9: 51,054,546 (GRCm39)	M1360L	probably benign	Het
Hspg2	T	C	4: 137,271,677 (GRCm39)	V2481A	possibly damaging	Het
Ifnl3	A	G	7: 28,223,283 (GRCm39)	K101E	probably benign	Het
Il15	A	T	8: 83,064,204 (GRCm39)	S77R	probably damaging	Het
Ints13	T	C	6: 146,476,216 (GRCm39)	D95G	probably damaging	Het
Kcmf1	G	A	6: 72,819,929 (GRCm39)	P357S	probably benign	Het
Kcmf1	G	T	6: 72,825,289 (GRCm39)	T268K	probably benign	Het
Kmt2d	A	T	15: 98,748,153 (GRCm39)	I3057N	unknown	Het
Lgi2	A	G	5: 52,695,832 (GRCm39)	F376L	probably damaging	Het
Lrig3	T	G	10: 125,832,993 (GRCm39)	L289R	probably damaging	Het
Mafk	A	G	5: 139,785,876 (GRCm39)	S25G	probably benign	Het
Mpz	T	C	1: 170,987,204 (GRCm39)		probably null	Het
Nalcn	A	C	14: 123,515,761 (GRCm39)	I1680R	probably benign	Het
Or13d1	C	T	4: 52,971,470 (GRCm39)	P283L	probably damaging	Het
Or5ak24	T	A	2: 85,260,902 (GRCm39)	K90N	probably benign	Het
Or5g26	C	T	2: 85,494,518 (GRCm39)	V87M	possibly damaging	Het
Or5p62	A	T	7: 107,771,701 (GRCm39)	N83K	probably benign	Het
Otof	A	C	5: 30,528,912 (GRCm39)	I1827S	possibly damaging	Het
Oxgr1	A	G	14: 120,259,614 (GRCm39)	Y198H	probably damaging	Het
P3h2	T	A	16: 25,784,559 (GRCm39)	N645I	probably damaging	Het
Pbld2	A	G	10: 62,889,691 (GRCm39)	T158A	probably benign	Het
Pdgfrb	C	T	18: 61,206,315 (GRCm39)	R608C	probably damaging	Het
Pdia5	T	C	16: 35,228,049 (GRCm39)	T408A	probably benign	Het
Pik3cg	A	G	12: 32,226,845 (GRCm39)	V1014A	probably benign	Het
Prpf8	A	G	11: 75,399,374 (GRCm39)	T2180A	probably damaging	Het
Rabgap1l	A	T	1: 160,551,742 (GRCm39)	Y245*	probably null	Het
Rerg	T	C	6: 137,044,033 (GRCm39)	T28A	possibly damaging	Het
Rhcg	A	G	7: 79,249,216 (GRCm39)	I335T	probably damaging	Het
Rmnd1	C	T	10: 4,353,873 (GRCm39)	V78I	probably damaging	Het
Ryr2	A	C	13: 11,664,662 (GRCm39)	V3547G	probably benign	Het
Serpinb6e	G	A	13: 34,016,698 (GRCm39)	T345I	probably damaging	Het
Smchd1	T	C	17: 71,668,955 (GRCm39)	T1687A	probably benign	Het
Smim45	A	T	15: 82,136,774 (GRCm39)		probably benign	Het
Speer4f2	A	C	5: 17,581,661 (GRCm39)	H201P		Het
Spef2	G	A	15: 9,725,257 (GRCm39)	R167C	probably damaging	Het
Srp68	A	G	11: 116,162,733 (GRCm39)		probably null	Het
Tbc1d14	A	T	5: 36,669,884 (GRCm39)	F455I	probably benign	Het
Tet3	A	G	6: 83,432,006 (GRCm39)	V10A	possibly damaging	Het
Tlr3	A	T	8: 45,850,810 (GRCm39)	S696T	probably benign	Het
Tmem63b	T	C	17: 45,978,709 (GRCm39)	N300S	probably benign	Het
Tmprss11g	T	C	5: 86,637,150 (GRCm39)	I328M	probably damaging	Het
Tpm3	C	T	3: 89,980,029 (GRCm39)		probably benign	Het
Trim28	T	A	7: 12,758,833 (GRCm39)	L63Q	probably damaging	Het
Unc5b	G	A	10: 60,613,265 (GRCm39)	R324C	probably damaging	Het
Vmn1r236	T	A	17: 21,507,204 (GRCm39)	N107K	possibly damaging	Het
Vmn2r88	A	G	14: 51,656,100 (GRCm39)	T770A		Het
Zcchc2	C	A	1: 105,958,211 (GRCm39)	P894Q	probably damaging	Het
Zfhx2	A	G	14: 55,303,229 (GRCm39)	V1585A	probably benign	Het

Other mutations in Scnn1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00227:Scnn1a	APN	6	125,315,342 (GRCm39)	missense	probably benign	0.11
IGL01793:Scnn1a	APN	6	125,320,666 (GRCm39)	missense	probably benign	0.03
IGL01992:Scnn1a	APN	6	125,315,900 (GRCm39)	critical splice donor site	probably null
IGL03280:Scnn1a	APN	6	125,319,744 (GRCm39)	splice site	probably benign
scylla	UTSW	6	125,320,208 (GRCm39)	missense	probably damaging	0.98
R0086:Scnn1a	UTSW	6	125,319,550 (GRCm39)	splice site	probably benign
R0442:Scnn1a	UTSW	6	125,316,100 (GRCm39)	missense	probably damaging	1.00
R0454:Scnn1a	UTSW	6	125,299,189 (GRCm39)	missense	probably damaging	1.00
R0578:Scnn1a	UTSW	6	125,299,207 (GRCm39)	missense	probably damaging	0.97
R1538:Scnn1a	UTSW	6	125,315,856 (GRCm39)	missense	possibly damaging	0.48
R1579:Scnn1a	UTSW	6	125,299,103 (GRCm39)	missense	probably damaging	1.00
R1803:Scnn1a	UTSW	6	125,309,157 (GRCm39)	missense	probably damaging	0.98
R1876:Scnn1a	UTSW	6	125,315,801 (GRCm39)	missense	probably benign	0.05
R2113:Scnn1a	UTSW	6	125,314,774 (GRCm39)	missense	possibly damaging	0.60
R2178:Scnn1a	UTSW	6	125,307,965 (GRCm39)	missense	probably damaging	0.96
R2960:Scnn1a	UTSW	6	125,299,256 (GRCm39)	missense	probably damaging	1.00
R4072:Scnn1a	UTSW	6	125,315,870 (GRCm39)	missense	probably damaging	1.00
R4603:Scnn1a	UTSW	6	125,299,123 (GRCm39)	missense	probably damaging	1.00
R4928:Scnn1a	UTSW	6	125,299,136 (GRCm39)	missense	probably damaging	1.00
R5436:Scnn1a	UTSW	6	125,319,985 (GRCm39)	missense	possibly damaging	0.94
R6812:Scnn1a	UTSW	6	125,314,819 (GRCm39)	missense	probably benign	0.09
R8371:Scnn1a	UTSW	6	125,320,806 (GRCm39)	missense	possibly damaging	0.83
R8372:Scnn1a	UTSW	6	125,320,681 (GRCm39)	missense	probably damaging	0.96
R8841:Scnn1a	UTSW	6	125,320,208 (GRCm39)	missense	probably damaging	0.98
R9509:Scnn1a	UTSW	6	125,319,604 (GRCm39)	missense	probably damaging	0.99
X0026:Scnn1a	UTSW	6	125,299,073 (GRCm39)	missense	probably damaging	1.00
Z1176:Scnn1a	UTSW	6	125,320,855 (GRCm39)	missense	probably damaging	0.96

Predicted Primers

PCR Primer
(F):5'- TAGGTCTACTTCCCAGTGCTG -3'
(R):5'- ACCTTTCCAGAATGGCGAGAG -3'

Sequencing Primer
(F):5'- TACTTCCCAGTGCTGTGCAGG -3'
(R):5'- CAGCATCTCTAGACTGTAAGGCTG -3'

Posted On

2019-05-15